Photoreceptor Cell Death in FAS-Receptor Deficient Mice Following Experimental Retinal Detachment

Abstract

Purpose:: Photoreceptor cell death following retinal detachment occurs via activation of apoptosis, or programmed cell death, rather than by necrotic cell death. Retinal detachment upregulates and activates the FAS/FAS-ligand pathway, surface membrane proteins of the tumor necrosis factor-α superfamily, prior to activation of the intrinsic pathway of apoptosis. In this project, an experimental model of retinal detachment in mice eyes is used to compare the extent of photoreceptor cell death in FAS-receptor deficient and wild-type mice.

Methods:: Retinal detachments were created in FAS-receptor deficient lpr mice and C57 control mice by injecting 10% hyaluronic acid into the subretinal space using a transvitreous approach. One eye was left untreated as a control. Eyes were enucleated at 3 and 7 days, and fixed in 4% paraformaldehyde-PBS. Terminal dUTP-biotin nick end-labeling (TUNEL) was performed to assay for morphologic features associated with apoptosis.

Results:: TUNEL-staining was positive in the outer nuclear layer only in the detached portions of retina. The FAS-deficient lpr mice exhibited on average 75% less photoreceptor cell loss following retinal detachment than did the control mice at 3 days. There was no significant TUNEL staining in either the experimental lpr mice or the control C57 mice at 7 days.

Conclusions:: FAS-deficient lpr mice exhibit less photoreceptor cell death following experimental retinal detachment than do control mice at 3 days. This reduced level of apoptosis was seen in the genetic absence of the FAS pathway, despite the presence of an intact intrinsic pathway. With further research, preventing the upregulation or directly inhibiting the FAS/FAS-ligand pathway may provide a therapeutic target for preventing photoreceptor cell loss following in vivo retinal detachment.

Keywords: retinal detachment • apoptosis/cell death