Progressive Rod Degeneration in a Miniature Pig Model of Retinitis Pigmentosa

Abstract

Purpose: : We have developed a model of retinitis pigmentosa (RP) using somatic cell nuclear transfer with the most common rhodopsin mutation in autosomal dominant RP (Pro23His) in an inbred miniature pig. The aim of this study is to characterize the progression of retinal degeneration in the P23H pig retina during the period of maximum photoreceptor degeneration; thus, contributing useful data for exploiting this novel pig eye model and providing a biomedical model that is ideal for therapeutic interventions involving cell transplantation and other therapies.

Methods: : Pig eyes were examined and monitored using ophthalmoscopy, fundus photography, fluorescein angiography and OCT from postnatal day 1 (P1) to 21 months of age. Retinal degeneration was assessed by histology and immunocytochemistry of rod and cone photoreceptor markers. Photoreceptor cell apototosis was examined using TUNNEL staining.

Results: : Photoreceptor cell death was evident at P1, and OCT demonstrated marked retinal thinning at 21 months; H&E staining of retinal sections demonstrated that only one row of photoreceptors remained in the outer nuclear layer at this time. Immunohistochemistry demonstrated a progressive loss of rod photoreceptors between P1 and 21 months of age. And, at 21 months of age, cones comprised the single row of photoreceptors remaining.

Conclusions: : The P23H miniature pig displays progressive loss of rod photoreceptors mimicking what is observed in RP patients. Thus, these transgenic pigs represent a large animal model of rod photoreceptor loss which can be used in future studies of cell transplantation or other therapies for retinal repair.

Keywords: retina • degenerations/dystrophies • photoreceptors