Protective Role of Soluble FasL in Photoreceptor Cell Loss

Abstract

Purpose: : Retinal detachment is characterized by photoreceptor loss and thinning of the retinal outer nuclear layer. FasL has been shown to mediate apoptotic cell death after retinal detachment. It exists in two forms, the membranous Fas Ligand (mFasL) that is thought to have proapoptotic activity and the soluble form of FasL (sFasL) that is thought to have pro-survival and anti-inflammatory properties. We wanted to investigate the role of soluble FasL in photoreceptor degeneration using the rodent model of retinal detachment.

Methods: : Wild-type and membrane-only FasL transgenic mice, also known as ΔCS, where the cleavage site in exon 2 of FasL was mutated were used. Experimental retinal detachment was created by subretinal injection of hyaluronic acid. Cell death was evaluated using TUNEL staining. Photoreceptor survival was assessed by measuring the relative thickness of the outer nuclear layer in histological sections. Levels of selected death and inflammatory cytokines were measured by ELISA.

Results: : Three days after retinal detachment, the normalized thickness of the outer nuclear layer decreased to 0.65 ± 0.09 in the no soluble FasL animals compared to 0.79 ± 0.09 (P = 0.002) in the wild type animals. TUNEL-positive cells in the detached retina of ΔCS animals were 2196 ± 215 comparing to, 1538 ± 107 in the WT (P = 0.013), after 3 days. The TNF-α levels were not significantly affected in the ΔCS animals.

Conclusions: : Absence of soluble FasL seems to potentiate photoreceptor cell loss in a rodent model of RD. Interfering with Fas signaling may have potential therapeutic effects in neurodegenerative retinal conditions

Keywords: retinal detachment • apoptosis/cell death • neuroprotection