Genetic evaluation in age related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field (the macula) because of damage to the retina. It occurs in two forms: 1-Dry (nonexudative), cellular debris called drusen accumulate between the retina and the choroid, and the retina can become detached. 2-Wet(exudative), which is more severe, blood vessels grow up from the choroid behind the retina, and the retina can also become detached. It is a major cause of blindness and visual impairment in older adults (>50 years). Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced agerelated macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration. Notable progress has been made in understanding the genetic pathogenesis of ocular diseases and improving the safety and specificity of vector-based ocular gene transfer methods. Preliminary successes have been reported in phase 1 clinical trials utilising PEDF gene therapy for AMD. Given the success of antiVEGF therapy using monoclonal antibody and the positive results seen for anti-VEGF gene therapy.