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JL Dunaief, T Dentchev, A Milam; Evidence for Apoptosis in Age-Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2817.
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Purpose: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly, yet much needs to be learned about the pathogenesis. The goal of this study is to shed light on the mechanism of cell death in AMD. Methods: Post mortem eyes from nine normal controls and ten donors with AMD including six with geographic atrophy (GA), three with exudative AMD and one with drusen only and were examined for evidence of apoptosis using the TUNEL technique. TUNEL positive cells in each retinal layer were quantified. Following TUNEL labeling, sections were processed for immunocytochemistry with antibodies specific for rods, cones, or Fas receptor (CD95). Results: AMD eyes had significantly more TUNEL positive cells than controls in the RPE, PR, and INL layers. In GA, the TUNEL positive cells were greatest in number near edges of atrophy and were labeled with an anti-rod antibody. TUNEL positive cells in the INL were mainly in the inner aspect of the layer. Fas receptor immunoreactivity was greater in photoreceptors from AMD eyes than in controls. Conclusion: These data support a role for apoptosis in RPE, PR and INL cell death in AMD. In GA cases, we find clustered TUNEL positive rods near edges of atrophy, where cell death would be anticipated. TUNEL positive RPE and INL cells provide evidence for apoptotic death in these layers. Increased Fas receptor immunoreactivity in AMD cases implicates the Fas/FasL system as a possible trigger of cell death in AMD. These studies should suggest potential points of pharmacological intervention for AMD.
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