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Joshua L. Dunaief, MD, PhD; Tzvete Dentchev, MD; Gui-Shuang Ying, MS; Ann H. Milam, PhD

Arch Ophthalmol. 2002;120:1435-1442.

Objective  To investigate apoptosis in human age-related macular degeneration (AMD).

Methods  Postmortem retinas with AMD and normal retinas were studied by terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) to identify dying cells, and by immunocytochemistry with cell-specific antibodies to identify rods and cones. Sections were also labeled for Fas, a cell surface receptor that triggers apoptosis in other cell types. The maculas with AMD had geographic atrophy (GA) or exudative AMD.

Results  Maculas with AMD had statistically significant increases in TUNEL-positive cells in the inner choroid, retinal pigment epithelium (RPE), photoreceptors, and inner nuclear layers compared with normal retinas. In eyes with GA, TUNEL-positive rod and RPE cell nuclei were present near edges of RPE atrophy. Photoreceptors in the maculas of eyes with AMD were strongly Fas-positive, while normal photoreceptors were only weakly labeled.

Conclusions  Evidence in this study suggests that in human AMD, RPE, photoreceptors, and inner nuclear layer cells die by apoptosis. Most TUNEL-positive RPE and photoreceptor cells were at edges of atrophy, correlating with clinically observed expansion of atrophic areas with vision loss in patients with GA. Increased Fas labeling in AMD photoreceptors indicates that the Fas/Fas ligand system may be involved in photoreceptor apoptosis. This information is essential for developing rational therapy for AMD.

From the F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia.

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