Evaluation of the State of the Blood-Retinal Barrier during the Development of Signs of Age-Related Macular Degeneration in OXYS Rats

Abstract

Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease that is becoming the leading cause of irreversible vision loss in people over 55 years of age. The development of the wet form of AMD is associated with impaired permeability of the blood-retinal barrier (BRB). It was believed that the BRB does not change in the dry form of the disease, but it was recently shown that dysfunction of the BRB may also contribute to its development; however, information about the state of the BRB at different stages of AMD, especially preclinical ones, is limited. The purpose of this study was to assess the possible contribution of changes in BRB permeability to the development of signs of AMD in OXYS rats, a model of the dry form of the disease. During the period when clinical signs of AMD in OXYS rats are absent (age 20 days) and during their manifestation (~5 months) and progression (at 12 and 18 months), the permeability of the BRB for Evans blue dye and the retinal contents of the tight junction proteins occludin, claudin-5, and zonula occludens-1 (ZO-1) were assessed. Wistar rats of the same age served as controls. In OXYS rats, a decrease in the permeability of the BRB was detected, which may result in a violation of the trophic supply of the retina as well as an increase in the level of occludin during the progression of signs of AMD. ZO-1 level decreased with age, but no interstrain differences were detected. Analysis of retinal transcriptomes (RNA-seq data) showed that changes in the expression of genes included (according to KEGG) in the category of tight junctions are maximum in the period from 20 days to 3 months in rats of both strains. In OXYS rats, the mRNA levels of the Dlg1, Cd1d1, Map3k5, and Arhgef2 genes at the age of 3 months and the Crb3, F11r, Cgn, Cd1d1, and Rap2c genes at the age of 18 months are different compared to Wistar rats. Such changes in gene expression in the retina of OXYS rats as AMD signs develop indicate the activation of compensatory mechanisms.