Role of the Fas-signaling pathway in photoreceptor neuroprotection.

Published

Journal Article

OBJECTIVE: To determine whether inhibiting the Fas proapoptosis pathway will result in increased photoreceptor survival after separation of the retina from the retinal pigment epithelium (RPE). METHODS: Retina/RPE separation was induced in rat and mouse eyes by the subretinal injection of hyaluronic acid, 1%. Fas-pathway signaling was inhibited by the concomitant injection of a Fas receptor-neutralizing antibody, small inhibitory RNA against the Fas-receptor transcript (siFAS), or the use of the Fas-receptor defective mouse strain LPR. Indices of photoreceptor death included terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, cell counts, and retinal thickness measurements. Retinas were immunostained with antibodies against rhodopsin and cone opsin to evaluate rod and cone photopigment production, respectively. RESULTS: Inhibition of Fas signaling using Fas receptor-neutralizing antibody, siFas, or LPR mice resulted in a significant reduction in the number of TUNEL-positive photoreceptor cells as well as in a significant preservation of outer nuclear layer cell counts and thickness as compared with retina/RPE separation in eyes with intact Fas signaling. Fas-pathway inhibition resulted in preservation of both rhodopsin- and cone opsin-positive cells. CONCLUSIONS: Inhibition of the Fas proapoptosis pathway results in significant photoreceptor preservation after retinal separation from the RPE. CLINICAL RELEVANCE: Fas-pathway inhibition might serve as a novel mechanism for preserving photoreceptor cells during retinal disease.

Full Text

Duke Authors

Cited Authors

  • Zacks, DN; Boehlke, C; Richards, A-L; Zheng, Q-D

Published Date

  • October 2007

Published In

Volume / Issue

  • 125 / 10

Start / End Page

  • 1389 - 1395

PubMed ID

  • 17923548

Pubmed Central ID

  • 17923548

International Standard Serial Number (ISSN)

  • 0003-9950

Digital Object Identifier (DOI)

  • 10.1001/archopht.125.10.1389

Language

  • eng

Conference Location

  • United States