Morphological and Functional Changes in the Retina after Chronic Oxygen-Induced Retinopathy

Shinsuke Nakamura,Hiromi Ogishima,Kazuhiro Tsuruma,Hideaki Hara,Shunsuke Imai,Masamitsu Shimazawa,Steven Barnes

doi:10.1371/journal.pone.0032167

Shinsuke Nakamura, Hiromi Ogishima + Show 5 more

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https://doi.org/10.1371/journal.pone.0032167

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Journal: PloS one	Publication Date: Feb 14, 2012
Citations: 89	License type: CC BY 4.0

Affiliation: Gifu Pharmaceutical University

Abstract

The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment.

Highlights

Retinopathy of prematurity (ROP) is a disease that affects the retinas of premature infants
Retinal damage To investigate the damage in each retinal layer after exposure to high levels of oxygen during infancy, we evaluated the number of cells in the the ganglion cell layer (GCL) and the thicknesses of the inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL)
The main results of the present ROP study can be summarized as follows: (1) there were deficits in oscillatory potential (OP), which are useful indices of IPL dysfunction; (2) retinal damage was found primarily in both the IPL and INL where many retinal blood vessels exist; (3) retinal vascular permeability increased via breakdown of the barrier properties in retinal blood vessels

Summary

Introduction

Retinopathy of prematurity (ROP) is a disease that affects the retinas of premature infants. The key pathological change, namely, retinal neovascularization, is associated with local ischemia followed by the subsequent development of neovascularization. In the more severe forms of the disease, the abnormal vascular changes may progress to retinal detachment. The prognosis for recovery of good visual acuity is poor. ROP is the leading cause of preventable childhood retinal dysfunction. The World Health Organization’s Vision 2020 programme targets ROP as an avoidable disease requiring early detection and treatment to prevent blindness [1]

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