Functional and morphological alterations of older rhodopsin P347L transgenic rabbits

Abstract

Purpose: A rhodopsin P347L transgenic (Tg) rabbit, a model of retinitis pigmentosa, has been generated in our laboratory. We have reported the functional and morphological alterations of this animal until 12-months-of-age (Kondo M et al. 2009, IOVS). The purpose of this study was to evaluate the functional and morphological changes of older Tg rabbits.

Methods: We studied 25 Tg and 5 wild type (WT) rabbits of New Zealand White background whose ages ranged from 18 to 60 months. Full-field ERGs were recorded to determine when the ERGs became non-recordable in Tg rabbits. Spectral-domain optical coherent tomography (SD-OCT) was used to measure the retinal thickness of 6 Tg rabbits and 5 WT rabbits at 3-years-of-age. The histological changes of the retina in Tg and WT rabbits were examined by light and electron microscopy after the ERGs became non-recordable.

Results: The ERGs of Tg rabbits became non-recordable between 30 and 54 months, and all were non-recordable by 54-months-of-age. SD-OCT showed that the retinal thickness was not reduced in the Tg rabbits at 3-years-of-age in spite of the photoreceptor degeneration. This indicated a thickening of the inner retina in these Tg rabbits. Histological analysis of the Tg rabbits after the ERGs became non-recordable showed that the photoreceptors were totally degenerated. However, the structure of the inner nuclear and ganglion cell layers were highly disorganized with a proliferation of glial cells.

Conclusions: Our results showed that it took less than 54 months for the ERGs to be non-recordable in this Tg rabbit. We found that retinal remodeling with glial cell proliferation was one of the features of this rabbit model at an advanced stage of retinal degeneration.