RGD Reference Report - Role of the Fas-signaling pathway in photoreceptor neuroprotection. - Rat Genome Database

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Role of the Fas-signaling pathway in photoreceptor neuroprotection.

Authors: Zacks, DN  Boehlke, C  Richards, AL  Zheng, QD 
Citation: Zacks DN, etal., Arch Ophthalmol. 2007 Oct;125(10):1389-95.
RGD ID: 8662409
Pubmed: PMID:17923548   (View Abstract at PubMed)
DOI: DOI:10.1001/archopht.125.10.1389   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinal detachment treatmentISOFas (Rattus norvegicus)8662409; 8662409 RGD 
retinal detachment treatmentIMP 8662409 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fas  (Fas cell surface death receptor)

Genes (Mus musculus)
Fas  (Fas cell surface death receptor)

Genes (Homo sapiens)
FAS  (Fas cell surface death receptor)


Additional Information