Mitochondrial DNA and Vision Loss

DNA, mitochondria and eye health

Every one of your cells contains hundreds of mitochondria, the energy-producing organelles that reduce oxygen molecules to water and store energy in the ATP molecule, the universal energy storage molecule.  A single mitochondrion contains several loops of DNA, each of which includes 37 genes involved in energy generation. Mitochondrial DNA and mutations in mitochondrial genes are inherited from mothers. They have been linked to devastating degenerative disorders, including serious ocular diseases.

Scientists have known since 1963 that mitochondria in humans have mutations that occur between ten to seventeen more than mutations to nuclear DNA. In 1980 Miquel and co-workers in fact published the first mitochondrial DNA mutation theory of aging. 

Errors in mitochondrial genes were not linked to human diseases until 1988. Emory University researchers traced young-adult blindness, Leber’s hereditary optic neuropathy, to a small inherited mutation in one mitochondrial gene. In that same year, the Institute of Neurology in London connected the deletion of relatively large segments of mitochondrial DNA to progressive muscle disorders.

As a high energy-producing organ, the eye is particularly susceptible to the consequences of mitochondrial damage. Mitochondria are a major site of oxidative stress caused by excess free radical production. Mitochondrial dysfunction is increasingly implicated in ophthalmologic diseases of aging, including glaucomaage-related macular degeneration and diabetic retinopathy.

Several proteins were recently identified that play a role in the mitochondrial oxidative stress response within retinal cells, and these proteins may be therapeutic targets for common ophthalmologic disorders.   

Oxidative damage that results over time from mitochondrial DNA ( mtDNA) instability leads to an accumulation of mitochondrial damage, which is now seen as an important pathogenic factor in age-related ophthalmologic disorders such as diabetic retinopathy, age-related macular degeneration, and glaucoma.

The mitochondrion regulates cell death (apoptosis) and is believed to be responsible for neuronal loss in neurodegenerative diseases. Evidence is mounting that mitochondria are responsible for the regulation of cell death in glaucoma.

The development of diabetic retinopathy occurs slowly in about 50% of type I diabetes patients and approximately 10% of type II diabetic patients within 15 years of diagnosis.

Pigmentary retinopathy is a hereditary degenerative disease of the retina and its typical symptoms are night blindness, pigmentary changes in the retina and loss of vision.  The most common mitochondrial DNA disease in which pigmentary retinopathy may be seen is Neurogenic weakness, Ataxia, and Retinitis Pigmentosa.

Diabetic retinopathy is the number one cause of blindness in young adults. The development of diabetic retinopathy involves progressive damage to retinal mitochondria caused by high blood sugar, or hyperglycemia. Antioxidant therapy, such as the overproduction of the main mitochondrial enzyme, manganese superoxide dismutase (MnSOD), reduces mitochondrial damage and inhibits the development of diabetic retinopathy.

Age-Related Macular Degeneration is mainly caused by damage to the retinal ganglion cells and is made worse by mitochondrial dysfunction caused by sunlight (UVA and UVB). In one study, retinal and blood mitochondrial DNA were compared between AMD patients and a healthy control group. The researchers discovered that retinal cells had more mitochondrial DNA rearrangements and deletions than the healthy controls.  Mitochondrial DNA alterations accumulate over time in retinal ganglion cells caused by oxidative stress, an imbalance between free radicals and the retinyl cells antioxidant defenses.

Glaucoma is the number two cause of blindness worldwide. Glaucoma involves damage to the optic nerve which is loaded with mitochondria, making it especially susceptible to impairment of mitochondrial respiratory function. Mitochondrial function can be caused by mutations in mitochondrial genes, intraocular pressure, or sunlight-induced oxidative stress.