Rod-Derived Cone Viability Factor (RdCVF) Expression in Normal Human Retina and Age-Related Macular Degeneration

Abstract

Purpose:: Age-related Macular Degeneration (AMD) is a complex and multifactorial both polygenic and environmental disorder. Although most histopathologic and clinical studies incriminate Retinal Pigment Epithelium cells as the primary site of lesions in AMD, several studies point toward early rod photoreceptor loss at the level the rod-enriched perifoveal ring (Curcio et al., 1993, 1996; Scholl et al., 2004). Rod damage would lead to a decrease in rod-derived cone viability factor release such as RdCVF expression and to a subsequent loss of cone photoreceptors in the fovea. To document this hypothesis, we studied RdCVF expression in normal and age-related macular degeneration retinas.

Methods:: Paraffin sections of the macular region from three patients with pre-mortem documented history of age-related macular degeneration and three age-matched controls were included in this study. In the age-related macular degeneration group, one patient had early age-related maculopathy with drusen and two had late-stage disease including one with geographic atrophy and one with choroidal neovascularization. Polyclonal antibodies were generated against human RdCVF. Immunostaining with these antibodies was correlated with Rhodopsin immunostaining and hematoxylin-eosine coloration. In parallel, in situ hybridization was performed against RdCVF mRNA and was compared with in situ hybridization towards Rhodopsin mRNA.

Results:: RdCVF immunostaining in human normal and age-related macular degeneration retinas was localized in the outer nuclear layer and in the interphotoreceptor matrix as previously reported in the mouse retina (Léveillard et al. 2004). In situ hybridization showed similar results with restricted staining of the anti-sense RdCVF probe to the outer nuclear layer. Preliminary qualitative analysis of normal and age-related macular degeneration retinas would suggest a decrease in RdCVF expression in the disease group.

Conclusions:: This study confirms that RdCVF is expressed in normal human retina and age-related macular degeneration at the level of the photoreceptors. It also suggests that RdCVF expression is decreased in AMD.

Keywords: retina • growth factors/growth factor receptors • age-related macular degeneration