What Causes Stargardt's Disease?
Stargardt's disease, specifically the STGD1 form, is caused by a mutation that occurs on the short arm of chromosome 1p21-22 in the ABCA4 gene.
In order for a person to inherit a mutation in this gene, both parents would have to be carriers of a copy of this gene.
In STDG1, the genetic defect manifests itself in the visual phototransduction cycle, which is the process by which light is changed into electrical signals in the photoreceptor cells (rod cells, cone cells, and photosensitive ganglion cells) of the retina of the eye. These electrical signals stimulate biological processes in the brain that allow the brain to be able to see images. This cycle is what allows a person to be able to see.
When there is a mutation in this gene, this cycle becomes disrupted as ATP becomes defective, and therefore cannot provide energy to allow this process to fully complete itself. The body produces a protein which blocks normal transportation of food and waste to the retina's photoreceptor cells.
This causes rapid formation of a byproduct of this cycle to build up in the retina as without ATP providing energy to the cycle, the cycle is never able to complete itself and get to a point where it clears out the byproduct of the retina. This deposition of byproduct can have harmful affects as it is a waste product building up in the retina.
The byproduct of the phototransduction cycle are toxic vitamin A dimers, also known as bisretinoids. When this cycle does not come to completion, these bisretinoids build up in fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina, which is the nutritional support layer for the rods and cones of the retina. Lipofuscin is composed of N-retinylidene-N-retinyl-ethanolamine, also known as A2E. A major component of what makes up this chemical is vitamin A. Vitamin A is known to be critical for vision as vitamin A supports and allows essential processes that allow the retinal receptors, conjunctival membranes, and cornea to work properly, allowing a person to see. However, having too much preformed Vitamin A in the body can become toxic. When too much of this byproduct of the phototransduction cycle, which is essentially preformed vitamin A, builds up in the Retinal Pigmented Epithelium, the RPE and the rods and cones break down in the presence of these waste deposits, killing the photoreceptor cells, causing a person to go blind.
When a person has Stargardt's disease and this cycle is disrupted, over time, more and more preformed vitamin A will build up in the eye. This buildup in the retina will become toxic, and as more of it gathers over time, more and more photoreceptor cells will die over time, causing a person to gradually go blind by losing a significant amount of their central vision.
In order for a person to inherit a mutation in this gene, both parents would have to be carriers of a copy of this gene.
In STDG1, the genetic defect manifests itself in the visual phototransduction cycle, which is the process by which light is changed into electrical signals in the photoreceptor cells (rod cells, cone cells, and photosensitive ganglion cells) of the retina of the eye. These electrical signals stimulate biological processes in the brain that allow the brain to be able to see images. This cycle is what allows a person to be able to see.
When there is a mutation in this gene, this cycle becomes disrupted as ATP becomes defective, and therefore cannot provide energy to allow this process to fully complete itself. The body produces a protein which blocks normal transportation of food and waste to the retina's photoreceptor cells.
This causes rapid formation of a byproduct of this cycle to build up in the retina as without ATP providing energy to the cycle, the cycle is never able to complete itself and get to a point where it clears out the byproduct of the retina. This deposition of byproduct can have harmful affects as it is a waste product building up in the retina.
The byproduct of the phototransduction cycle are toxic vitamin A dimers, also known as bisretinoids. When this cycle does not come to completion, these bisretinoids build up in fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina, which is the nutritional support layer for the rods and cones of the retina. Lipofuscin is composed of N-retinylidene-N-retinyl-ethanolamine, also known as A2E. A major component of what makes up this chemical is vitamin A. Vitamin A is known to be critical for vision as vitamin A supports and allows essential processes that allow the retinal receptors, conjunctival membranes, and cornea to work properly, allowing a person to see. However, having too much preformed Vitamin A in the body can become toxic. When too much of this byproduct of the phototransduction cycle, which is essentially preformed vitamin A, builds up in the Retinal Pigmented Epithelium, the RPE and the rods and cones break down in the presence of these waste deposits, killing the photoreceptor cells, causing a person to go blind.
When a person has Stargardt's disease and this cycle is disrupted, over time, more and more preformed vitamin A will build up in the eye. This buildup in the retina will become toxic, and as more of it gathers over time, more and more photoreceptor cells will die over time, causing a person to gradually go blind by losing a significant amount of their central vision.