Progressive Central Photoreceptor damages and Retinal Pigment Epithelium Abnormalities in Oxygen Induced Retinopathy

Abstract

Purpose: : Retinopathy of Prematurity (ROP) is the leading cause of neonatal blindness in high and mid income countries. Characterized by abnormal retinal vascular development, ROP is a complex condition associate with central retinal function loss. Our previous study demonstrates pronounced and sustained central choroid vascular involution in animal models of ROP. Here we set out to understand the progression of central photoreceptor dysfunction, subretinal abnormalities and their potential correlation with the choroidal involution.

Methods: : The rat model of OIR exposing animals to 50%/10% oxygen interchanged every 24 hours from postnatal day (P) 1- P14 was used. Animals were then returned to room air for later development. Electron Microscopy (EM) and Immunohistochemistry staining of frozen sagittal sections were used to detect the localization and expression of proteins, and to identify structural changes. ELISA immunoassay was used to detect the superoxidase dismutase (SOD) activity and redox potential of the tissue. Real-time PCR was used to detect the RNA expression level of angiogenesis and inflammation related genes; western blot analysis was used to detect protein expression.

Results: : Progressive central photoreceptor degeneration was detected in OIR treated animals. Migration of activated glia cells was accompanied with the damaging photoreceptors. Retinal pigment epithelium (RPE) cells lost their distinct morphology at P90 but not during early development (P3-P18). At even later stage (i.e. P300), OIR animals exhibit a thinning of the RPE cells. Increase in thickness of Bruch’s membrane was also detected by EM. At P90, the OIR exposed choroidal tissue was under high oxidative stress indicated by over expression of SOD and oxidized redox potential. Increased production of IL-1R was detected in central choroid of OIR animals.

Conclusions: : Progressive photoreceptor degeneration and RPE damage in mid-age adulthood of the OIR animals was never demonstrated before. The association of central photoreceptor and RPE damage with central choroidal changes brought a novel insight in ROP related retinal function loss aside from retinal vasculopathy.

Keywords: retinopathy of prematurity • oxidation/oxidative or free radical damage • retinal pigment epithelium