Document Type

Journal Article

Date of this Version

1-2017

Publication Source

Investigative Ophthalmology & Visual Science

Volume

58

Issue

1

Start Page

270

Last Page

281

DOI

10.1167/iovs.16-20749

Abstract

Purpose

To characterize a light damage paradigm and establish structural and immunocytochemical measures of acute and protracted light-induced retinal degeneration in the rhodopsin (RHO) T4R dog model of RHO–autosomal dominant retinitis pigmentosa (ADRP).

Methods

Retinal light damage was induced in mutant dogs with a 1-minute exposure to various light intensities (0.1–1.0 mW/cm2) delivered with a Ganzfeld stimulator, or by fundus photography. Photoreceptor cell death was assessed by TUNEL assay, and alterations in retinal layers were examined by histology and immunohistochemistry 24 hours and 2 weeks after light exposure. Detailed topographic maps were made to document changes in the outer retinal layers of all four retinal quadrants 2 weeks post exposure.

Results

Twenty-four hours post light exposure, the severity of photoreceptor cell death was dose dependent. Immunohistochemical analysis revealed disruption of rod outer segments, focal loss of the RPE integrity, and an increase in expression of endothelin receptor B in Müller cells with the two highest doses of light and fundus photography. Two weeks after light exposure, persistence of photoreceptor death, thinning of the outer nuclear layer, and induction of Müller cell gliosis occurred with the highest doses of light.

Conclusions

We have characterized outcome measures of acute and continuing retinal degeneration in the RHO T4R dog following light exposure. These will be used to assess the molecular mechanisms of light-induced damage and rescue strategies in this large animal model of RHO-ADRP.

Copyright/Permission Statement

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords

retinal degeneration, light damage, rhodopsin, ADRP, canine model

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Date Posted:19 April 2018

This document has been peer reviewed.