Vision Loss Glossary

Achromatopsia is a type of cone dystrophy where there are normally problems only with vision from cone photoreceptors, the ones responsible for color and day vision and visual acuity. Therefore individuals mainly see by their rod cells, may be completely colorblind or almost colorblind, and have poor visual acuity. Individuals often experience extreme light sensitivity (photophobia). They also may have a variable degree of nystagmus (involuntary movement of the eyes). Other types of cone dystrophies may involve some degree of loss of rod cell vision.

see stem cell

Age-related macular degeneration (AMD) is a retinal degenerative disease that causes a progressive loss of central vision. AMD occurs due to degeneration of the macula, a small region in the center of the retina that’s rich in cones, the photoreceptors that enable a person to perceive fine details. There are two types of AMD, dry and wet, which progress in severity differently. In general, dry AMD is characterized by the presence of drusen—tiny deposits of protein and fat under the retina. While drusen can be present and not impact vision, certain types of drusen may interfere with the health of the macula, and lead to its degeneration. Geographic atrophy, or GA, is the term for late-stage dry AMD when drusen buildup has led to the death of retinal pigment epithelium (RPE) and photoreceptor cells such that a scotoma, or blind spot in the center of the eye, has developed and grown. In wet AMD, excess blood vessels grow beneath the macula when they shouldn’t. These vessels can leak fluid or blood and quickly damage the macula, leading to rapid changes in central vision if not treated. Dry AMD (without GA) can generally be thought of as early AMD, while wet AMD is a later stage case of the disease. Unlike inherited retinal disease, AMD does not have a direct genetic cause; instead, risk factors like age and habits like smoking are strongly implicated in whether AMD develops. A number of treatments are FDA approved to treat AMD, like EYELEA®, Lucentis®, and VABYSMO for wet AMD, and SYFOVRE® and IZERVAY® for GA.

Amblyopia is a type of poor vision that happens in just one eye. It develops when there’s a breakdown in how the brain and the eye work together, and the brain can’t recognize the sight from one eye. Over time, the brain relies more and more on the other, stronger eye — while vision in the weaker eye gets worse. Amblyopia starts in childhood, and it’s the most common cause of vision loss in kids. However, early treatment of amblyopia can be very effective at preventing long-term impacts to vision.

see age-related macular degeneration

Angiogenesis refers to the growth of new blood vessels. When uncontrolled, angiogenesis can cause destruction of the retina due to leakage of blood. When growing in places they shouldn’t, blood vessels can cause disease, such as wet age-related macular degeneration (AMD).

An antioxidant is a nutritional supplement (like vitamins C or E), drug, or naturally occurring product that protects cells from damage induced by light, stress or metabolic processes (called oxidation). Antioxidants are also prevalent in foods, such as vegetables and fruits.

Apoptosis is a controlled process for cell death, triggered by a signal or biochemical reaction, in response to an accumulation of cellular damage.

AREDS was a clinical study sponsored by the Federal government’s National Eye Institute that determined a specific nutritional supplementation regimen for slowing progress of vision loss in individuals with AMD. The AREDS supplementation is: Antioxidants (500 mg Vitamin C, 400 IU Vitamin E, 15 mg Beta-carotene) and Minerals (80 mg Zinc Oxide, 2mg Copper). Another study-AREDS II, started in October 2006-is designed to test modified minor adjustments to the original supplement combinations (e.g., removing beta-carotene from the formulation, lowering zinc), along with different dosages of lutein, zeaxanthin and/or omega-3 fatty acids. If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

AREDS was a series of clinical studies sponsored by the Federal government’s National Eye Institute designed to determine a specific nutritional supplementation regimen for slowing progress of vision loss in individuals with age-related macular degeneration (AMD). The resulting AREDS daily supplementation is included a number of vitamins and minerals. A follow-up study, AREDS 2, was then designed to test modified minor adjustments to the original supplement combinations, as well as the addition of omega-3 fatty acids, and ultimately was comprised of: 500mg vitamin C, 400 IU vitamin E, 2mg copper, 10mg lutein, 2 mg zeaxanthin and 80 mg zinc. There was found to be an incremental increase in benefit to the AREDS 2 supplementation compared to the initial AREDS regimen. This supplement formula can be purchased over-the-counter, however - if you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

Astigmatism is a common eye problem that can make your vision blurry or distorted. It happens when your cornea or lens has an imperfection in their curvature. Usually, you can correct mild to moderate astigmatism with eyeglasses or contact lenses.

An autosomal dominant disease is one passed through families by the autosomal dominant pattern of inheritance. In this type of inheritance, inheriting one gene copy with a disease-related mutation is sufficient to cause the disease, even if the other inherited copy of the gene is normal. In these cases, if the mother or the father has one mutated copy of the disease gene, then each of their children has a 50 percent chance (or 1 chance in 2) of inheriting the mutated copy of the gene needed to cause the disease.

An autosomal recessive disease is one passed through families by the autosomal recessive pattern of inheritance. In this type of inheritance both parents, called carriers, have one gene with a disease-related mutation paired with one normal copy of the gene. Each of their children then has a 25 percent chance (or 1 chance in 4) of inheriting both mutated copies of the gene (one from each parent) needed to cause the disease. Carriers are unaffected because they have only one copy of the gene.

An autosome is a chromosome (or DNA package) that does not play a primary role in determining a person’s sex (i.e., not an X or Y chromosome). Autosomal recessive and autosomal dominant diseases are caused by mutations in genes that reside on one of the 22 paired autosomes.

Bardet-biedl syndrome is a complex disorder that affects many parts of the body including the retina. Individuals with BBS have a retinal degeneration similar to retinitis pigmentosa (RP), and may also exhibit renal disease, polydactyly (extra fingers and toes), obesity and developmental disabilities.

see bardet-biedl syndrome

Best disease, also known as vitelliform macular dystrophy, is an inherited retinal disease which causes macular degeneration and loss of central vision, visual acuity, and color perception. Best disease is generally diagnosed in childhood or early adolescence, and is caused by mutations in the BEST1 gene inherited through an autosomal dominant fashion.

Beta-carotene is a nutritional pigment (and antioxidant) that can be used in the visual cycle of the eye. It is responsible for the orange color of carrots and other fruits and vegetables.

A Biologics License Application is a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce. This application needs to be submitted to and approved by the Food and Drug Administration (FDA) before a new biological product can be sold.

The Bruch’s membrane is the blood-retina barrier that separates the cells of the retinal pigment epithelium (RPE) from the choroid. This membrane is structurally similar to the blood-brain barrier, because the retina is an extension of the brain. A rupture of this barrier can cause diseases, like wet age-related macular degeneration (AMD), where the choroid blood vessels grow abnormally into the retina and cause damage, ultimately affecting vision.

Carotenoids encompass a large group of tetraterpenoid organic pigments that are naturally occurring, synthesized by and responsible for the coloring of many fruits and vegetables. Carotenoids can be synthesized fats and other basic organic metabolic building blocks. Beta-carotene is a type of carotenoid.

A cell is the smallest biological unit of specialized function capable of self-replication. A cell consists of an outer membrane (like a porous plastic bag), which encases the fluid of the cell, and the nucleus (a specialized compartment that contains the cell’s genetic material (DNA) and directs the production of proteins). Conversion of many cells (of either the same or different functions) at the same spot in the body can form an organ with specialized purposes, like the retina, liver or brain.

Research approaches focused on cellular and molecular mechanisms of disease seek to uncover how and why disease begins, and ultimately use this information to design an effective, targeted treatment. Cellular and Molecular Mechanisms of Disease is one of the Foundation’s six research priority areas. Scientists and clinicians are determining how mutations in each identified gene cause retinal degenerative disease and specifically what goes wrong in the cells of the eye as a result of that mutation. The resulting knowledge is being used to create effective, directed treatments.

The central nervous system (CNS) is the “central command system” of the body, and includes the brain, spine and retina. Every nerve outside of the blood-brain and blood-retina barriers is considered part of the peripheral nervous system. Since the retina is part of the CNS, it is possible that treatments for other neurodegenerative diseases of the CNS (like Lou Gehrig’s disease or Alzheimer’s disease) could work for or help us develop treatments for retinal degenerative diseases.

Choroideremia is a rare inherited disorder that causes progressive loss of vision due to degeneration of the choroid, as well as retinal pigment epithelium (RPE) cells and photoreceptors of the retina. Choroideremia is an X-linked disease, caused by mutations in the CHM gene.

A chromosome is a “package” of DNA that holds the genetic code to life. In humans, each non-sex cell has 23 pairs of chromosomes.

The ciliary body, located in a “ring” around the iris, is responsible for controlling the shape of the lens, via muscle connections to “fibers” attached to the lens, a process that controls how light focuses on the retina. In addition, it creates fluid (called aqueous humor) that provides nutrients to and takes waste away from the lens and the cornea. Glaucoma drugs target the ciliary body to lower aqueous humor production and cause a drop in the pressure inside the eye.

Cilia are very small, hair-like structures that are found in or on nearly all cells of the body, often developing a unique functional role on many specialized cell types (for example, photoreceptors, kidney, and lung cells). A mutation in a gene whose protein helps maintain the structure of these “hairs” can cause diseases with symptoms in one or more affected body systems, creating a syndrome. For example, some Bardet-biedl syndromes involve vision and kidney problems, caused by altered cilia proteins found in both photoreceptors and kidney cells.

Clinical: Structure and Function is one of the Foundation’s six research priority areas. Scientists and clinicians are developing improved technology and standardized processes to better establish the relationship between clinical retina structure and retina structure in the context of degenerative retinal diseases. This work will enable earlier and more accurate disease detection, with the goal of expanding the identified patient population that may be eligible to participate in clinical trials.

Cone cells are cone-shaped photoreceptors that detect light for vision. Although cones are present throughout the retina, they are mainly found in the macula (the central portion of the retina). Cone cells are particularly important for color and day vision and discriminating fine visual detail, like that required for discerning facial features or reading a book. Humans have three types of cone cells (blue, green and red) that respond to different wavelengths of light to make up the full rainbow of colors.

see achromatopsia

Cone-rod retinal dystrophy characteristically leads to early impairment of vision. An initial loss of color vision and of visual acuity (due to loss of cone photoreceptor function) is followed by nyctalopia (night blindness) and loss of peripheral visual fields (due to loss of rod photoreceptor function). In extreme cases, these progressive symptoms are accompanied by widespread, advancing retinal pigmentation and chorioretinal atrophy of the central and peripheral retina. For related but different diseases, see achromatopsia, cone dystrophy and rod-cone dystrophy.

Congenital stationary night blindness is an inherited eye disorder that is not progressive (“stationary”) and principally affects the rod photoreceptors in the retina, impairing night vision.

There may also be moderate to high myopia (short sightedness) for those with the disorder. The disorder is usually diagnosed by electroretinogram.

Copper is a mineral that is required for nutrition and proper functioning and maintenance of the body. Copper (2 mg) is one component of the AREDS 2 daily nutritional supplementation treatment to slow vision loss in age-related macular degeneration (AMD). If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

The cornea is the clear dome that covers the front of the eye. It starts to focus light onto the lens. If the eye is like a camera, consider the cornea to be like a UV (ultraviolet) filter screwed onto the end of the camera lens. This is the part of the eye that undergoes vision-correcting LASIK surgery.

A cortical implant is a device (e.g. a chip or cable) that is implanted into the visual cortex, the specific portion of the brain found at the back of the head that interprets visual information. This device would theoretically transmit to the cortex the visual images received from camera-like sunglasses (or another type of vision-detecting machine) worn by the user. The goal of this device is similar to a retinal prosthetic, but bypasses the retina and optic nerve completely, possibly restoring vision in patients who are completely blind.

see congenital stationary night blindness

DHA is a highly unsaturated fatty acid (a type of omega-3 fatty acid) that is found in foods (e.g., tuna, salmon) and dietary supplements, and is implicated in photoreceptor function. DHA is greatly concentrated in rod photoreceptor cells. Foundation-supported scientists have found that patients with some forms of retinitis pigmentosa (RP) and Usher syndrome have lowered serum levels of DHA. A number of clinical trials have been performed to test whether DHA used as a nutritional supplement can slow the progression of X-linked RP, the dominant form of Stargardt disease, Usher syndrome and age-related macular degeneration (AMD). However, while some results suggested slowed loss of visual field sensitivity, overall slowdown of disease did not occur. If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

DNA is a long chain of building-blocks (called nucleotide bases) that carries the genetic instructions (genes) for making living organisms. Each DNA building-block can be thought of as a “letter.” When there’s a gene mutation (or “spelling mistake” for even one letter), it can potentially create a non-functioning protein that causes disease. Each gene makes a messenger called RNA, which then is the template for making proteins, the actual workhorses of the cell. DNA is found in the nucleus of a cell where it is packaged into highly specific, long chains called chromosomes (there are 23 chromosome pairs in humans).

see DHA

see autosomal dominant disease

Think of donor-advised funds like a savings account for the sole purpose of charitable giving. Individuals, families, or groups contribute to their donor-advised fund that is managed by a sponsoring organization, such as a community foundation or financial institution. The donor gets an immediate tax break when they contribute funds to their DAF and can later suggest where their funds are granted out to. Essentially, DAFs act as a bridge between a donor’s money and the charities they want to support.

Drusen are yellow-white retinal deposits that may contain a mixture of proteins, pigments, fats and other wastes, and mainly concentrate around the macula. These deposits are associated with the dry form of age-related macular degeneration (AMD) and with some juvenile forms of macular degeneration, like Best disease and Stargardt disease. Scientists are still determining the exact composition and origin of drusen deposits, and how they can lead to retinal disease.

FDA is the acronym for the Food and Drug Administration, a branch of the United States (US) Department of Health and Human Services.

FFB is the acronym for Foundation Fighting Blindness.

A gene is a unit of inheritance, encoded by DNA. Genes are an organized sequence of building blocks for DNA (nucleotide bases or “letters”) that “spells out” the information necessary to create a specific messenger called RNA that, in turn, makes a specific protein. Every cell in the body has the same genetic “blueprint”; however, each organ uses a highly specialized combination of genes to produce proteins that are essential to the function and specialty of its particular cells. For example, in the eye, the genes ROM-1 and peripherin are important in forming the outer segment membranes of photoreceptor cells. Other proteins, like rhodopsin, are involved in a rod cell’s response to light. Any disruption in the function of the above-mentioned (and other) proteins can cause a retinal degenerative disease.

Gene mapping is the process of identifying a specific region (or locus) along one of the 23 paired chromosomes that contains a gene with a disease-causing mutation. This is also known scientifically as “positional cloning.” You can think of a region as a “neighborhood” and the gene that causes a disease as the “house” in that neighborhood. Once scientists have narrowed down the possibility to a particular locus/neighborhood on the chromosome, then they can identify the exact gene/house linked with that disease.

Gene therapy, or gene replacement therapy, is a therapeutic process that replaces or turns off the “bad” or mutated disease-causing gene, with the goal of restoring some level of normal protein function.

Generally, it is defined as the study of inheritance; in the context of retinal disease, it is the determination of genes linked with causing retinal degenerative diseases.

Genetics is one of the Foundation’s six research priority areas. Scientists and clinicians are looking for new genes linked to retinal degenerative diseases. It With over 300 inherited retinal disease or IRD-causing genes currently identified, it is thought that over half of disease-causing IRD genes have already been identified.

Genetic technologies are therapeutic processes that replace or turn off the “bad” or mutated disease-causing gene (or its RNA) and restore some level of normal protein function. Genetic Technologies is one of the Foundation’s six research priority areas and can be defined as the delivery of or modification to a gene or genetic information in cells for the purpose of achieving a therapeutic effect. Two common forms of genetic technologies that have shown promise in the treatment of retinal degenerative diseases are gene replacement therapy and antisense oligonucleotides, or ASOs. Gene replacement therapy is replacing the “bad” gene with the “good” form (i.e. the LCA treatment Luxturna®), and ASOs identify and bind to the “bad” RNA, either to fix its function or to mark it to be destroyed by existing cell defense processes.

Genetic testing or genotyping is the process of screening patients’ DNA samples to identify the specific gene and the specific mutation (spelling mistake) in a gene that causes a disease. The DNA samples are normally obtained by collecting a blood sample (since all cells of the body have the same genetic code). For more information on genotyping and how you can be tested, please obtain a copy of the Foundation’s Genetic Testing Information Packet on the FFB website. Scientists are attempting to connect the genotype (specific gene alteration or mutation) with the phenotype (physical and clinical symptoms) for every disease.

Geographic atrophy may be considered the end stage of dry age-related macular degeneration (AMD), causing severe vision loss. Over time, sometimes over many years, the atrophy of the retinal pigment epithelium (RPE) cells (due to drusen deposits in the retina) gets more prevalent until the entirety of the macula is affected.

On ophthalmological exams, geographic atrophy looks like a circle or spot of degeneration, in the central-most part of the retina. Also see age-related macular degeneration.

Gyrate atrophy is an autosomal recessively inherited disorder, which is due to a lack of the protein enzyme ornithine keto-acid aminotransferase (OAT), resulting in an increased blood serum level of ornithine (hyperornithinemia).

The symptoms of GA are progressive “night blindness” and peripheral vision loss.

The inner segment is one of the regions of a photoreceptor; specifically, it is the part of the photoreceptor cell that is closest to the front of the eye. In all vertebrates (animals with a spine), the inner segment serves not only as the site of energy production and oxidation, but also as a region of high refractive index (for light). The latter property causes the inner segment to act as a “waveguide” that channels light to the outer segment (where it is transformed into an electrical signal that travels down the optic nerve).

The United States Food and Drug Administration’s Investigational New Drug program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines before a marketing application for the drug has been approved.

The iris is the colored “ring” surrounding the pupil that regulates the amount of light that is admitted into the eye. If the eye is like a camera, consider the iris to be like an aperture.

see best disease; stargardt disease

Lancelot is the name of a Briard dog born blind due to a mutation in the RPE65 gene causing a dog-form of the human retinal degenerative disease called Leber congenital amaurosis (LCA). Lancelot was treated with gene therapy and could then see.

As reported in the scientific journal, Nature Genetics, in 2001, researchers injected into one of Lancelot’s eyes a “good” copy of the RPE65 gene that corrected his vision in that eye. Human clinical trials based upon this research in dogs began soon after these findings, ultimately leading to FDA approval of the RPE65 gene therapy treatment Luxturna®, the first gene therapy approved to treat an inherited retinal disease.

see Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is an inherited retinal degenerative disease characterized by severe loss of vision at birth. A variety of other eye-related abnormalities including roving eye movements, deep-set eyes, and sensitivity to bright light also occur with this disease. Some patients with LCA also experience central nervous system abnormalities. There are over 20 genes that have been identified that, when mutated, can cause LCA.

The lens is the oval-shaped, clear (transparent) part of the eye behind the cornea and iris that focuses incoming light onto the retina. If the eye is like a camera, consider the eye lens to be like a camera lens.

A locus is a location in one part of a chromosome where a particular gene(s) might reside, like a “house” (gene) might reside in a “neighborhood” (locus). Scientists who are looking for genes associated with retinal degenerative diseases call it a locus until they definitively prove that one (or more) gene(s) in this region cause(s) that disease.

Lutein and zeaxanthin are nutrient pigments that are abundant in green leafy vegetables and yellow and orange-colored fruits and vegetables. These pigmented carotenoids (the general term for nutrient pigments, of which lutein, zeaxanthin, and beta-carotene belong) are highly concentrated around the macula and provide its characteristic yellow appearance. Lutein and zeaxanthin are components of the AREDS 2 daily nutritional supplementation treatment to slow vision loss in age-related macular degeneration (AMD). If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

The macula is the central portion of the retina. The macula contains a dense concentration of cone photoreceptor cells that help us to see fine visual detail (see visual acuity), daylight and color vision. Only primates (including humans and monkeys) have a macula in their retina.

A Marketing Authorization Application is an application submitted by a drug manufacturer seeking marketing authorization, or permission to bring a medicinal product to the market. This term is primarily used in the EU.

Messenger RNA (mRNA) is the gene messenger that results from the transfer of genetic information from DNA into RNA. mRNA is the template for making a protein. Often the original mRNA requires processing (i.e., cutting and “re-glueing”) into a shorter mRNA template for production of the final, proper protein.

A metabolic process refers to methods used by the body to break down nutrients, using oxygen, and converting them into simple energy packets that the body can then use for maintaining cell functions necessary for life. Some waste products from this process include water and carbon dioxide. Oxidation (interaction between oxygen and all the different substances it may contact) is one part of the metabolic process; antioxidants help to control damage from too much oxidation. If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

A mutation is any change in the normal order of DNA “letters” (bases), or a “spelling mistake”, in the DNA, that defines a specific gene. A disease-causing mutation is one which either disrupts the process of making mRNA (see mRNA) or alters the activity of the protein coded by that gene sufficient to make it non-functional. For example, many different mutations in the rhodopsin gene may cause retinitis pigmentosa (RP).

NEI is the acronym for the National Eye Institute, a part of the research-funding government organization, the United States (US) National Institutes of Health.

The Food and Drug Administration’s New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing.

Novel medical therapies in the context of retinal disease involve delivering a protein or drug to the eye that prevents the photoreceptors and/or retinal pigment epithelium (RPE) cells from dying, thus saving vision.

Novel Medical Therapies is one of the Foundation’s six research priority areas. Scientists and clinicians are testing delivery of survival proteins or drugs to protect the photoreceptors and/or RPE cells from dying (or preventing loss of light-detection capability). This is an especially important priority area that is sometimes called a “cross-cutting advance,” since neuroprotective survival proteins or drugs could potentially treat many different retinal degenerative diseases.

The nucleus is the specialized compartment within a cell that houses the DNA, packaged as chromosomes. The nucleus is also the location where RNA (messenger RNA) is made from genes and transported out of the nucleus to serve as a template for protein production.

Nutritional and environmental therapies in the context of retinal disease include clinically-tested nutritional supplements or lifestyle changes that have been proven to slow or stop the loss of vision.

Nystagmus is a constant, rapid and involuntary oscillation of the eyes

Nystagmus can be caused by a number of physiological problems, including issues with balance, eye muscles or fixation of vision. The eye movement can be side to side, up-down and/or circular. Individuals with Leber congenital amaurosis (LCA) may have nystagmus due to an inability to fixate their vision from an early age.

Omega-3 fatty acids are types of fat that are important for cell processes. The term “omega” refers to the specific configuration of chemical “double-bonds” and thus predicts the shape of the fat. There are many types of omega-3 fats that can be obtained from a number of food sources, including EPA (eicosapentaenoic acid; found in cold water fish and algae) and DHA (docosahexanoic acid; found in cold water fish and algae; see DHA) and ALA (alpha-linolenic acid; found in some vegetable oils and nuts). Omega-3 fatty acids are components of the AREDS 2 daily nutritional supplementation treatment to slow vision loss in age-related macular degeneration (AMD). If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

The optic nerve is the bundle of nerve cells, or “cable”, that receives the light detection signals from other retinal cells (photoreceptors initially detect the photons of light) and transports them to the part of the brain called the visual cortex where they are processed. A person doesn’t actually “see” until their visual cortex processes the signals. If the eye is a digital camera, consider this to be like the cable used to download the images from the camera onto a computer.

Optogenetics is the scientific technique of introducing a light-sensitive protein (historically isolated from algae) into cells that are not naturally responsive to light. With this method, expression of an optogenetic protein in a cell results in the cell becoming active when light hits it. In the context of retinal disease, optogenetics is being tested as a way to restore light sensitivity to the retina. In late stage retinal disease when the light sensitive cells of the eye, the photoreceptors, have died, optogenetics may be able to imbue the remaining cells of the retina with the ability to detect light, and restore some vision. There are a number of clinical trials currently testing optogenetic methods as treatments for retinal degenerative disease.

The outer segment is one of the regions of a photoreceptor; specifically, it is the part of the photoreceptor cell that is directly adjacent to retinal pigment epithelium (RPE) cells, near the back of the retina. The outer segment is responsible for the conversion of light into electrical signals, via the visual cycle.

Specifically, it is the last part of the photoreceptor that light passes through on its first pass (i.e., before any reflections) through the retina. Outer segments are composed of stacked disks (think of a stack of pancakes) that are flattened in planes perpendicular to the path of the light. The proteins involved with the visual cycle are found in the outer segments and convert light into electrical energy transmitted to the optic nerve.

Oxidation is the interaction between oxygen molecules and all the different substances they may contact. Oxidative stress can occur when there’s a metabolic imbalance between the production of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or easily repair the resulting damage to a cell. This damage may promote apoptosis, which may cause retinal degenerative disease. Certain antioxidants can protect a cell from this damage. If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

The peripheral nervous system (PNS) encompasses all nerves that are not part of the brain, spinal cord or retina (although the cell bodies (control centers) for nerves that extend into the extremities (including arms and legs) are anchored in the brain and spinal cord). The PNS is not protected by bone or the blood-brain barrier, leaving it exposed to toxins and mechanical injuries. Normally, peripheral nerves either control voluntary muscle movement (i.e., controllable processes like lifting an arm) or are involved in involuntary processes, like breathing, heart rate, etc. The retina is not considered to be part of the PNS.

Phagocytosis is the cell’s process of engulfing solid particles by the cell membrane, forming an internal “food vacuole” or “sack”. This sack is internalized and the contents are subsequently degraded and either released or retained for recycling. Some retinal degenerative diseases (e.g., some forms of Stargardt disease) are thought to be caused by problems with this phagocytosis. About 10% of the outer segment tips of photoreceptor cells are phagocytosed every day by retinal pigment epithelium (RPE) cells.

A phenotype consists of the observable characteristics or clinical symptoms present in an individual with a particular retinal degenerative disease. Scientists are attempting to correlate the phenotype with the genotype for every retinal degenerative disease (see genetic testing).

Photoreceptor cells are the light sensitive cells in the retina that absorb light and convert it into an electrical signal that is passed to the brain through the optic nerve (see phototransduction). There are two types of photoreceptor cells: rod and cone cells. Rod cells are responsible for black-and-white, peripheral and night vision. Cone cells are mainly responsible for fine visual detail (see visual acuity, color, central and day vision. Humans have three types of cone cells, each of which detects colored light of a different wavelength (red, green and blue). In humans, rod cells are mainly found in the retinal periphery while cone cells are concentrated in the central portion of the retina (macula). Toxins, produced as byproducts of light detection by photoreceptor cells, are removed and/or recycled by the adjacent retinal pigment epithelium (RPE) cells.

Phototransduction is also called the visual cycle. It is the cascade of biochemical reactions involved in detecting light and converting it to an electrical signal that is relayed to the brain via the optic nerve. Both photoreceptors and retinal pigment epithelium (RPE) cells are essential for this process. Problems with proteins involved in phototransduction are responsible for causing certain retinal degenerative diseases.

A proof of principle is a scientific confirmation that a previously unproven idea or experimental therapy actually works (for instance, a drug produces a therapeutic effect in an animal model(s)). Proof of principle provides the first measurable evidence that an experimental therapy might also work in humans.

see autosomal recessive disease

Restorative therapies in the context of retinal disease involve strategies to rescue or replace dead or dying retinal cells, optimize visual prostheses, and develop proteins that can return light sensitivity to the retina after degeneration (see optogenetics). Restorative Therapies is one of the Foundation’s six research priority areas. Scientists and clinicians are testing treatments for retinal degenerative diseases with stem cell and retinal transplants, visual prosthetics, and optogenetics therapies. These therapies have the potential to treat all retinal degenerative diseases, even in those people who have completely lost all photoreceptor and/or retinal pigment epithelium (RPE) cells.

The retina is a thin layer of light-detecting cells at the back of the eye.

If the eye is a camera, consider the retina to be like the film or digital sensor. The retina contains several nerve cell types that are considered to be an extension of the brain, and thus part of the central nervous system. The cell types and structures that comprise the retina include: photoreceptor nerve cells (rods and cones); other types of nerve cells that relay phototransduction signals to the optic nerve “cable” (horizontal, bipolar, amacrine, ganglion, Müller cells); retinal vessels; retinal pigment epithelium (RPE) cells; Bruch’s membrane. The photoreceptor cells of the retina absorb light and convert this light into electrical signals (see phototransduction). The electrical signals are transferred from the photoreceptors to other, secondary nerve cells (listed above) which then send the electrical signals through the optic nerve to the visual cortex region of the brain for interpretation.

The retinal pigment epithelium (RPE) is a very thin, pigmented cell layer found directly beneath the photoreceptor cells. RPE cells sit between the photoreceptor cell layer of the retina and the Bruch’s membrane and choroid. The RPE obtains nutrients and oxygen from the choroid and provides them to the photoreceptor cells, while also carrying away waste products from photoreceptor cells for disposal to the choroid. In addition, RPE cells recycle proteins and other components involved in the phototransduction process and provide other survival proteins to the retina. RPE cells phagocytose or “chew up” the ends of photoreceptor outer segments every day as a “preemptive strike” to prevent damage from built-up waste products.

A retinal prosthetic is an implantable device that electrically stimulates the retina with information that it receives from a secondary light detection device (i.e., camera glasses) worn by the user.

Retinal transplantation involves injecting a layer of cells (already composed of photoreceptor and/or retinal pigment epithelium (RPE) cells) into the retina, near the macula, with the purpose of replacing dead or dying retina cells. There are two ways that retinal transplantation could improve vision: 1) the transplanted, healthy photoreceptor and RPE cells integrate into existing retina and signal through the optic nerve to the brain; 2) the transplants slow or stop the progression of the disease (either with or without integration into the retina) by producing survival proteins that keep remaining photoreceptor cells from dying and improve their detection of light and/or transmission of signals. A number of clinical trials utilizing this method are currently underway.

Retinal vessels are the vessels found on top of the retina at the back of the eye that look like “tree branches” when viewed by an ophthalmologist during an eye exam. These vessels become damaged and leaky during eye diseases like diabetic retinopathy, retinopathy of prematurity and other diseases.

Retinitis pigmentosa (RP) refers to a group of inherited diseases causing retinal degeneration.

Most forms of RP are characterized by the initial breakdown of rod cells. Sometimes called rod-cone dystrophy, RP usually begin with night blindness, as rods are important for vision in dark conditions. RP is typically diagnosed in adolescents and young adults. It is a progressive disorder, often progressing to impact cone cells as well. The rate of progression and degree of visual loss varies from person to person. RP can be inherited in a dominant, recessive or X-linked fashion, and there are over 90 genes that have been identified to cause RP.

Retinoschisis is vision loss due to the splitting of retinal layers and retinal deterioration due to a mutation in the retinoschisin (RS1) gene.

The RS1 protein is thought to act like a “glue” to hold together the retina. RS1 is an X-linked gene, where it is normally males who show symptoms of this disease. In addition to visible degeneration of the retina, the electroretinogram (ERG) is a negative (b-wave more reduced than a-wave).

Rhodopsin is a light-detecting component (a visual pigment) of rod photoreceptor cells composed of a protein called opsin that is chemically linked to a processed fragment of vitamin A. Rhodopsin resides in the outer segments of rod photoreceptor cells (near the retinal pigment epithelium (RPE) cells) and can only be formed in the dark. When light strikes, the rhodopsin molecule changes shape, generating the initial signal in the visual process. Ultimately, the vitamin A fragment splits off from the opsin protein to be recycled by the RPE cells and brought back to the photoreceptor outer segments, where it can be reattached to opsin in the dark. This series of reactions in light and dark is called the visual cycle (or phototransduction).

RNA comprises a family of gene products derived from DNA whose most common member, messenger RNA (mRNA), is used as a template for making protein. Scientists and clinicians are currently testing approaches that target mRNA in many treatments for retinal degenerative diseases.

A rod cell is a rod-shaped photoreceptor cell that is located throughout the retina but is more common outside of the central macular region of the retina (i.e., is found in the periphery of the retina). The rod cell is particularly important for black and white, night and peripheral (side) vision. In many forms of retinitis pigmentosa (RP), rod cell loss leads to what is sometimes referred to as “tunnel vision.”

Rod-cone dystrophy results from a primary loss of rod photoreceptors, followed by loss of cones. The term, rod-cone dystrophy is used as an ‘umbrella term’ to imply retinal defects that impact primarily rod cells, with cone cells spared, at least until later stages of the disease. It can be used to generically define any retinal degenerative disease that exhibits this condition. Retinitis pigmentosa (RP) is considered a rod cone dystrophy, as is Leber Congenital Amaurosis (LCA) and Usher syndrome. Note that rod-cone dystrophy is a different disease entity than cone-rod dystrophy.

see retinitis pigmentosa

see retinal pigment epithelium

The sclera, also called the “white of the eye” is the tough outer protective shell of the eye. If the eye is like a camera, consider the sclera to be like the camera body.

The sex chromosomes are the X and Y chromosomes inherited from a biological mother and father. The inherited combination of X and Y chromosomes determine the sex of the baby. Normally, a female inherits two X chromosomes (one from each parent) and a male inherits one X chromosome from his mother and one Y chromosome from his father. There are some genes on the X chromosome that, when mutated, will cause particular types of X-linked retinal degenerative diseases.

Stargardt disease is the most common form of inherited juvenile macular degeneration. The progressive vision loss associated with Stargardt disease is caused by the death of photoreceptor cells in the central portion of the retina called the macula.

Also involved in Stargardt disease is a region beneath the macula called the retinal pigment epithelium (RPE). Peripheral vision is usually preserved. Stargardt disease typically develops during childhood and adolescence, and is almost always caused by mutations in the ABCA4 gene. Since mutations in certain genes may cause the build-up of a toxin called A2E (a break-down product of vitamin A), vitamin A dietary supplementation is not recommended for some individuals with Stargardt disease. If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines. For information on another juvenile macular degeneration, see Best Disease.

A stem cell is a primitive, unspecialized cell that has the capacity to self-regenerate, but develops a highly specialized function when grown in the appropriate environment and treated with specific proteins or survival factors. In other words, it’s a cell that “hasn’t decided what it wants to be when it grows up.” Stem cells in the human retina have been found in the ciliary body, a specialized structure that sits on either side of the iris, near the retina. These ciliary stem cells usually lie dormant in the adult. These and other stem cells have now been isolated by many scientific groups and are being evaluated as a potential source for replacement of retinal pigment epithelium (RPE) and photoreceptor cells. There are many different types of stem cells, including adult and embryonic stem cells. Adult stem cells are from mature tissue that can renew itself but has a limited ability to transform into specialized cell types (i.e., fewer cell options). Embryonic stem cells, being from early stages of development, have the theoretical potential to produce any kind of cell in the body.

Strabismus is a misalignment of the eyes in which each eye can simultaneously point in a different direction. Crossed eyes (esotropia) are one type of strabismus; “wall-eyes” (exotropia) are another. The exact cause is unknown, but it appears to be a problem with the eye muscles. Strabismus can affect depth perception.

Also see restorative therapies.

Survival factors are drugs or biologically-occurring proteins that promote the health of nerve cells, such as photoreceptors. There are many different types of survival factors. Examples include, ciliary neurotrophic factor (CNTF), pigment epithelium-derived factor (PEDF), basic fibroblast growth factor (bFGF), glial-derived neurotrophic factor (GDNF), and rod-derived cone viability factor (rdCVF). RdCVF is a survival factor/protein that is currently being assessed used in clinical trials for retinitis pigmentosa (RP) and rod-cone dystrophy.

Trans fats are unhealthy types of fat that may increase the risk of developing age-related macular degeneration (AMD). These are chemically-modified fats that increase the shelf life of the products to which they are added. The FDA requires that companies list the amount of trans fats, which may also be referred to as “hydrogenated” or “partially hydrogenated” fats or oils in ingredient lists, in the food labels of product. Please consult with your personal physician and ophthalmologist before making any nutritional or lifestyle changes, as your personal health situation may require monitoring or a non-typical approach.

Ultraviolet (UV) light is part of the light/radiation that comes from the sun, with a wavelength shorter than that of visible light, but longer than soft X-rays. There are approximately three types of UV light: UVA (wavelengths of 400-315 nm), also called Long Wave or “blacklight”; UVB (wavelengths of 315-280 nm), also called Medium Wave; and UVC (wavelength less than 280 nm), also called Short Wave or “germicidal” (because it kills pathogenic organisms on exposed surfaces). UV Light will damage the retina (as well as the skin) with lengthy, unprotected exposure. To protect your eyes, it is recommended that you wear sunglasses that block all forms of UV light. This is particularly important for those who have retinal degenerative diseases, because their retinas may be more susceptible to damage or vision loss from exposure to UV light (depending on the nature of their disease).

There are many different types of this dietary fat - some have been linked to positive health effects (see DHA; docosahexaenoic acid) while others have been linked to a risk of developing cardiovascular disease and age-related macular degeneration (AMD) (see trans fats).

Usher syndrome is an inherited condition characterized by hearing impairment and progressive vision loss. Balance may also be affected. Symptoms vary from person to person and progress at different rates.

There are at least three different forms of Usher syndrome. People with Usher syndrome type 1 (USH1) are born completely deaf and experience problems with balance. The first signs of retinitis pigmentosa (RP) - night blindness and loss of peripheral vision - usually appear in early adolescence.

In Usher syndrome type 2 (USH2), newborns have moderate to severe hearing impairment. Symptoms of RP typically start shortly after adolescence. Visual problems progress less rapidly than in Usher type 1 and hearing loss usually remains stable.

A rarer third type of Usher syndrome (USH3) was first documented in 1995. Children with USH3 are usually born with good or only mild impairment of hearing. Their hearing and vision loss is progressive, starting around puberty. Balance may be affected.

Hearing loss in Usher syndrome is due to a genetic mutation (alteration) affecting nerve cells in the cochlea, a sound-transmitting structure of the inner ear. The same genetic defect also adversely affects photoreceptor cells in the retina, leading to vision loss. Usher syndrome genes code for proteins that support cellular structures important for the function of both photoreceptors and cochlea cells. This may explain why one individual may have both vision and hearing problems.

For another disease where a mutation causes damage to cilia photoreceptor cells as well as cells in other organ systems, see Bardet-Biedl-Syndrome.

A vector is the vehicle for delivering genes or genetic information into the nucleus of a cell. In the case of retinal gene therapy, vectors act like a fleet of microscopic delivery trucks transporting new, therapeutic (“good”) genes into retinal cells. Most vectors are modified forms of viruses (a “safe” form). Viruses are extremely effective at getting inside a cell; however, viruses also contain elements that may damage cells. Researchers have worked to genetically modify viruses used as vectors to be safe and have few immune side effects, without compromising their delivery capabilities. Examples of such viral vectors include: lentiviral vectors and adeno-associated vectors (AAV).The FDA approved gene therapy Luxturna® for LCA (RPE65) utilizes a retina-specific AAV vector.

VEGF is comprised of a class of proteins that cause new blood vessel growth (angiogenesis), which are needed for normal body functions, like development, wound repair and the menstrual cycle. It is thought that abnormally high levels of VEGF (or its presence in places where it shouldn’t be expressed) causes diseases characterized by blood vessel overgrowth, like wet age-related macular degeneration (AMD). Several anti-VEGF targeted treatments are being used for treatment of wet AMD (as well as several other diseases that have unwanted blood vessel growth, like colon cancer), including the drugs Avastin® and Lucentis®.

Visual acuity is the clarity of vision held by an individual and is measured as a fraction of normal vision: 20/20 vision indicates an eye that sees at 20 feet what a normal, “standard” eye should see at 20 feet; 20/400 vision indicates an eye that sees at 20 feet what a normal eye sees at 400 feet. Usually measured with a letter chart (Snellen), it can also be measured using pictures, black and white lines or visual evoked potentials.

see phototransduction

The visual field is the entire area that the eye can see in all directions without physically moving the eyes or head (fixed forward gaze), (including peripheral vision). Visual field is measured by a perimetry test. The typical field of vision for a human is about 140 degrees for each eye (monocular vision) and about 180 degrees for both eyes (binocular vision).

Vitamin C is an antioxidant found in certain fruits and vegetables (and as a commercial supplement) that is used by the body for a number of functions, including in the process of phototransduction. Vitamin C is one component of the AREDS 2 daily nutritional supplementation treatment to slow vision loss in age-related macular degeneration (AMD). If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

Vitamin E is an antioxidant found in certain oils, nuts, and other foods (and as a commercial supplement) that is used by the body for a number of functions. Vitamin E is one component of the AREDS 2 daily nutritional supplementation treatment to slow vision loss in age-related macular degeneration (AMD). If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.

The vitreous is the clear, jelly-like substance found in the middle of the eye that helps to regulate eye pressure and shape. Light must pass through the vitreous to fall upon the retina, so it must be as transparent as possible to avoid vision distortion or disruption.

A wavelength is a measure of the character of light, where certain wavelength ranges define and distinguish different “types” of light. The photoreceptor cell detects and chemically converts light of certain wavelengths within the visible range (between 400-700 nanometers or nm) into electrical signals that travel, via the optic nerve, to the visual cortex in the brain.

An X chromosome is part of the inherited packageof DNA that contains genes that help to determine the sex of an individual. Of the 23 pairs of chromosomes that humans carry in each cell of their body (except egg and sperm cells), genes on a single pair of chromosomes (called X and Y) determine sex. A mother can only give the X chromosome to her offspring (children), because females have two X chromosomes (XX), while fathers can give either an X or a Y chromosome to an offspring, because males have one X and one Y chromosome (XY). Importantly, the X chromosome also contains many genes that have nothing to do with determination of sex. Mutations in genes on the X chromosome result in diseases that are transmitted to male offspring (who have a single X-chromosome) only from their biological mother (maternal inheritance), or to female offspring from their mother or father (maternal or paternal inheritance). These are called X-linked diseases. In most cases, male offspring are affected by X-linked disease while females may either be unaffected carriers or may be affected with an X-linked disease.

see X chromosome

see retinoschisis

see retinoschisis

A Y chromosome is part of the inherited package of DNA that contains genes that help to determine the sex of an individual. Of the 23 pairs of chromosomes that humans carry in each cell of their body (except egg and sperm cells), genes on a single pair of chromosomes (called X and Y) determine sex. The Y chromosome is the sex chromosome passed-down from biological father to son that contains genetic instructions that give men their sex (and other body characteristics). Males inherit one Y chromosome from their father and one X chromosome from their mother, and are therefore normally symptomatic if they have an X-linked disease. So far, there are no known retinal degenerative diseases linked to the Y chromosome.

see lutein and zeaxanthin

Zinc is a mineral that is required for nutrition and proper function and maintenance of the body. Zinc oxide (80 mg) is one component of the AREDS 2 daily nutritional supplementation treatment to slow vision loss in age-related macular degeneration (AMD). If you use nutritional supplementation, please consult with your personal physician and ophthalmologist as your personal health situation may require monitoring or a non-typical approach and nutritional supplements may interfere with prescribed medicines.