Age-related macular degeneration: genetic and environmental factors of disease

Abstract

Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as the population ages; however, treatment options remain limited because the etiology and pathogenesis of AMD are incompletely defined. Recently, much progress has been made in gene discovery and mechanistic studies, which clearly indicate that AMD involves the interaction of multiple genetic and environmental factors. The identification of genes that have a substantial impact on the risk for AMD is not only facilitating the diagnosis and screening of populations at risk but is also elucidating key molecular pathways of pathogenesis. Pharmacogenetic studies of treatment responsiveness among patients with the "wet" form of AMD are increasingly proving to be clinically relevant; pharmacogenetic approaches hold great promise for both identifying patients with the best chance for vision recovery as well as tailoring individualized therapies.

Figure 1

The retina revealed. A. Diagrammatic representation of the retina. Inset shows the several types of neuronal cells within the macula, the retinal pigment epithelium (RPE), and choroid. B. Two optical coherence tomography images of a normal (left) and AMD retina with pigmented epithelium detachment (PED) (right).

Figure 2

Fundus images from patients representing several AMD subtypes. A. Normal macula. B. Macula with confluent soft drusen (black arrows), a hallmark of early AMD. C. Macula of dry AMD with soft drusen (black arrows) and geographic atrophy GA (white arrows). D. Macula of choroidal neovascularization (CNV) or wet AMD with subretinal hemorrhage (black arrows).

Figure 3

AMD risk profile as a function of disease-associated genes and smoking status. Joint effect of specific alleles of CFH (rs1061170, Y402H), HTRA1 (rs11200638), C3 (rs2230199) and smoking status were shown by odds ratios calculated by a logistic regression model, adjusted for age, gender, and body mass index (BMI).

Figure 4

Lifelong risk for developing AMD. Probabilities of developing advanced AMD were estimated by evaluating genotypes of CFH (rs2274170) and smoking status. Low risk, median risk, and high risk associated with CFH genotypes were coded as blue, purple, and red, respectively. Solid lines represent smoking group and dashed lines represent nonsmoking group.