Age related macular degeneration and mitochondrial dysfunction

See ((macular degeneration)).

Mitochondrial dysfunction induced by environmental toxicants may be an important risk factor in the etiology of dry age-related macular degeneration.

Age-related macular degeneration (AMD) accounts for 54% of all blindness in Americans of European ancestry.

ARMD accounts for 5% of all blindness globally.

It affects 30% of people over the age of 65 and is the most common cause of blindness in the elderly.

Prevalence of AMD estimated to be 6.5%, and costs the United States more than $51 billion a year in medical expenses and lost worker productivity.

Incidence growing.

A progressive degenerative disorder of the macula in which central vision becomes impaired.

There are two subtypes of AMD: early and late.

Early AMD is characterized by moderate to severe lipid-rich, sub–retinal pigment epithelium (RPE) deposits ref2242ed to as drusen and pigment abnormalities.

Late-stage AMD is often subdivided into degenerative loss of the photoreceptors, RPE, and choriocapillaris and neovascular AMD which is subretinal invasion of pathologic new vessels.

The drusen and geographic atrophy stages of AMD are collectively termed dry AMD.

The etiology of dry AMD has not been clearly resolved.

AMD pathogenesis is multifactorial, and it includes aging, genetic abnormalities,systemic health, environmental risk factors including cigarette smoking and mitochondrial dysfunction.

No effective treatment is available for dry AMD.

No known treatment exists that causes the regression of drusen or prevents their progression to geographic atrophy.

Mitochondria are intracellular organelles necessary for cell function and survival.

Mitochondria are crucial for the synthesis of adenosine triphosphate (ATP), the major form of cellular energy.

Major structures of mitochondria include the inner and outer mitochondrial membranes, cristae, and electron transport chain (ETC).

Cardiolipin (CL), a unique phospholipid exclusive to mitochondria and present only in the inner membrane of mitochondria (IMM), acts to hold together the respiratory protein complex subunits (complexes I, II, III, and IV) of the ETC that are essential to achieve optimal functioning of numerous enzymes involved in mitochondrial energy metabolism.

Cardiolipin is susceptible to peroxidation, leading to loss of its biophysical properties that support the electron transport chain.

Abnormal function of the electron transport train drives mitochondrial dysfunction, defined as loss of ATP synthesis, coupled with pathologic production of reactive oxygen species (ROS), especially superoxide, and loss of transmembrane potential of the inner membrane of mitochondria.

Mitochondrial dysfunction has been implicated in the etiology of dry AMD.

Mitochondria are located along the basal retinal pigment epithelium near drusen.

Mitochondrial dysmorphology is observed in retinal pigment epithelium in eyes with AMD

Mitochondrial DNA from these eyes demonstrate increased oxidative damage.

A genetic disease with mitochondrial DNA mutation, maternally-inherited diabetes and deafness (MIDD), is associated with an AMD-like maculopathy.

Cigarette smoking is the most important environmental risk factor for dry AMD onset and progression,

A major chemical toxicant in tobacco tar, hydroquinone (HQ), is a potential biochemical cause of retinal pigment epithelial cellular injury inducing drusen and geographic atrophy.

Retinal epithelial pigment mitochondria are a major target of HQ in the eye,

HQ exposure induces acute and chronic mitochondrial dysfunction resulting in biochemical and cellular changes consistent with dry AMD.


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