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.
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 LPRmice 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.
Authors: Cagri G Besirli; Nicholas D Chinskey; Qiong-Duan Zheng; David N Zacks Journal: Invest Ophthalmol Vis Sci Date: 2011-06-13 Impact factor: 4.799
Authors: George Trichonas; Yusuke Murakami; Aristomenis Thanos; Yuki Morizane; Maki Kayama; Christine M Debouck; Toshio Hisatomi; Joan W Miller; Demetrios G Vavvas Journal: Proc Natl Acad Sci U S A Date: 2010-11-22 Impact factor: 11.205
Authors: Mercy Pawar; Boris Busov; Aaruran Chandrasekhar; Jingyu Yao; David N Zacks; Cagri G Besirli Journal: Cell Death Differ Date: 2017-07-14 Impact factor: 15.828
Authors: Mi In Roh; Yusuke Murakami; Aristomenis Thanos; Demetrios G Vavvas; Joan W Miller Journal: Invest Ophthalmol Vis Sci Date: 2011-06-01 Impact factor: 4.799