“increasing intracellular concentrations of either tyrosine or L-DOPA both result in an increase in melanogenesis” or formation of the black pigment melanin. Thus there appears to be an association between reduced L-DOPA production and white skin. As suggested by the Figure and information in this section, reduced L-DOPA, resulting in white skin, appears to be associated with an increased risk of macular degeneration for white individuals over the age of 80. Environment and lifestyle
Smoking: Smoking tobacco increases the risk of AMD by two to three times that of someone who has never smoked, and may be the most important modifiable factor in its prevention. A review of previous studies found "a strong association between current smoking and AMD. ... Cigarette smoking is likely to have toxic effects on the retina." Hypertension (high blood pressure): In the ALIENOR study 2013, early and late AMD were not significantly associated with systolic or diastolic blood pressure (BP), hypertension, or use of antihypertensive medications, but elevated pulse pressure [(PP) systolic BP minus diastolic BP] was significantly associated with an increased risk of late AMD. Atherosclerosis
High cholesterol: Elevated cholesterol may increase the risk of AMD
Obesity: Abdominal obesity is a risk factor, especially among men
Fat intake: Consuming high amounts of certain fats, including saturated fats, trans fats, and omega-6 fatty acids, likely contributes to AMD, while monounsaturated fats are potentially protective. In particular, omega-3 fatty acids may decrease the risk of AMD.
performed a screen on 402 AMD patients and revealed a statistically significant correlation between mutations in fibulin-5 and incidence of the disease. Mitochondrial-related gene polymorphisms such as that in the MT-ND2 molecule, predicts wet AMD. Pathophysiology
The pathogenesis of age-related macular degeneration is not well known, although some theories have been put forward, including oxidative stress, mitochondrial dysfunction, and inflammatory processes. The imbalance between the production of damaged cellular components and degradation leads to the accumulation of harmful products, for example, intracellular lipofuscin and extracellular drusen. Incipient atrophy is demarcated by areas of retinal pigment epithelium (RPE) thinning or depigmentation that precede geographic atrophy in the early stages of AMD. In advanced stages of AMD, atrophy of the RPE (geographic atrophy) and/or development of new blood vessels (neovascularization) result in the death of photoreceptors and central vision loss. In the dry (nonexudative) form, drusen accumulates between the retina and the choroid, causing atrophy and scarring to the retina. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging. Early work demonstrated a family of immune mediators was plentiful in drusen. Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced.