Retinal Dystrophy Resulting From Ablation of RXR Alpha in the Mouse Retinal Pigment Epithelium

Abstract

Abstract: : Purpose To clarify the roles of retinoid X receptor (RXR) α in the retinal pigment epithelium (RPE) in vivo by cell type-specific gene targeting using the Cre/loxP system. Methods RXRα was selectively ablated in the RPE by crossing mice carrying a RPE-specific Cre transgene (Mori et al. IOVS 2002;43:1384–1388) and those with a floxed RXRα gene. The resulting mutant (RXRα ^rpe-/-) mice were studied with electroretinogram (ERG), histology, and immunohistochemstry for vision-related proteins expressed in the RPE and photoreceptor cells. Results RXRα ^rpe-/- mice showed (i) ~50% responses in both scotopic and photopic ERGs and delayed dark adaptation after photo-bleach; (ii) disorganization and flattening of the RPE cells; (iii) decrease in the number of photoreceptor cells with shorter and disorganized outer segments; (iv) reduced expression of RPE65, RGR, and CRALBP proteins in the RPE; and (v) little changes in expression of rhodopsin and cone blue and red/green pigments in the photoreceptor cells. Conclusion RXRα is required for normal RPE maturation and function which is essential for photoreceptor cell function and survival. Similarities of ocular phenotypes between RXRα ^rpe-/- mice and patients with age-related maculopathy raise the possibility that impairment of RXRα signaling could be involved in the pathogenesis of this disease.

Keywords: retinal pigment epithelium • retinoids/retinoid binding proteins • pathology: experimental