Course of loss of photoreceptor function and progressive Müller cell gliosis in rhodopsin P347L transgenic rabbits

Shinji Ueno; Taro Kominami; Satoshi Okado; Daiki Inooka; Mineo Kondo; Hiroko Terasaki

doi:10.1016/j.exer.2019.04.026

Course of loss of photoreceptor function and progressive Müller cell gliosis in rhodopsin P347L transgenic rabbits

Exp Eye Res. 2019 Jul:184:192-200. doi: 10.1016/j.exer.2019.04.026. Epub 2019 Apr 25.

Authors

Shinji Ueno¹, Taro Kominami², Satoshi Okado², Daiki Inooka², Mineo Kondo³, Hiroko Terasaki²

Affiliations

¹ Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: ueno@med.nagoya-u.ac.jp.
² Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
³ Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan.

PMID: 31029790
DOI: 10.1016/j.exer.2019.04.026

Abstract

Long living animal models of retinitis pigmentosa (RP) can provide important information on the retinal changes that occur at the late stages of photoreceptor degeneration. The rhodopsin Pro347Leu transgenic rabbit (P347L Tg) is a model of RP, and it has been used to analyze the functional and morphological changes in the retina following the degeneration of the photoreceptors. They have also been used to test newly-developed therapies to treat eyes with photoreceptor degeneration. However, assessments of the retinal changes in P347L Tg rabbits older than 1-year have not been reported even though the data are important for research on developing new therapies to restore vision at the end stages of RP. The purpose of this study was to determine the time course of the loss of photoreceptor function and the changes in the morphology of the retina of P347L Tg rabbits. The experiments were performed on 26 older P347L Tg rabbits. The results showed that the amplitudes of the ERGs of the P347L Tg rabbits gradually decreased and reached <10 μV between 30- and 54-months-of-age. Histological analysis at these later stages showed a loss of the photoreceptor layer, and OCT analysis showed absence of the layering of the retina. However, the thickness between the inner limiting membrane and the outer plexiform layer was about 1.7 times thicker than the corresponding thickness of WT rabbits in the OCT images. This thickening was caused by a marked gliosis of the entire retina which was confirmed by light and transmission electron microscopy. In addition, immunohistochemical analysis showed there was excessive staining of the glial fibrillary acid protein in the older P347L Tg rabbits although the rod ON bipolar cells and horizontal cells were still present in the inner nuclear layer. Our results indicate that the P347L Tg rabbit progressed to complete photoreceptor loss within 30- and 54-months-of-age and severe gliosis altered the morphology of the retina.

Keywords: Electroretinogram; Glial fibrillary acid protein; Optical coherence tomography; Retinal remodeling; Retinitis pigmentosa; Transgenic rabbit.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Ependymoglial Cells / pathology*
Gliosis / physiopathology*
Photoreceptor Cells, Vertebrate / pathology*
Photoreceptor Cells, Vertebrate / physiology
Rabbits
Retinitis Pigmentosa* / pathology
Retinitis Pigmentosa* / physiopathology
Rhodopsin / metabolism*

Substances

Rhodopsin