Abstract
Purpose :
While there is evidence that congenital blindness leads to structural and functional brain reorganisation, the impact of blindness on the vasculature in brain regions involved in vision is not well defined. This project aimed to fully characterise the vasculature along the visual pathway in both sighted and genetically blind mice. Immunohistochemistry-based techniques were used to quantify vascular density and integrity; glial and mural cell coverage; and expression of blood-brain barrier (BBB) components across several visuorecipient brain regions in wild-type (WT) mice and the rhodopsin knockout (Rho-/-) model of rod photoreceptor degeneration.
Methods :
Brain sections were obtained from 12-week old WT and Rho-/- mice, with regions of interest being located by staining with DAPI and comparing anatomical landmarks to the Allen Mouse Brain Reference Atlas. Sections were immunostained for the vascular marker isolectin-IB4; tight junction proteins claudin-5, occludin, and ZO-1; transporter proteins GLUT-1, P-gp, and LRP-1; the pericyte marker PDGFR-ß; the astrocyte marker GFAP; and the microglial marker IBA-1. Vascular density was quantified as the percentage area covered by isolectin-IB4 staining in images of brain regions of interest. Protein expression was quantified by normalising signal intensity for each marker to that of isolectin-IB4. The extravasation of a biotinylated agent (600 Da) and fibrinogen (340 kDa) was quantified as a proxy for BBB integrity.
Results :
A distinct profile of BBB protein expression; mural and glial cell coverage; and vascular integrity was observed between WT and Rho-/- mice and between brain regions along the visual pathway in each group. Notably, claudin-5, a key tight junction component, was detected at significantly higher levels in the visual cortex than in thalamic visuorecipient regions, such as the dLGN and the LP in WT mice, with similar trends being observed in Rho-/- group.
Conclusions :
Distinct BBB profiles along the visual pathway and between sighted and blind mice highlight the impact that the structural and functional brain reorganisation caused by blindness can have on the neurovascular unit. Given reports that visually impaired individuals are at increased risk of cognitive decline, these results highlight the vasculature as a possible contributing factor to this association, with altered vascular profiles leading to downstream neuronal dysfunction.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.