Retinal vasculature in hypertension

NIH RePORTER · NIH · R01 · $365,000 · view on reporter.nih.gov ↗

Abstract

Approximately 32-44% of the adult US population has hypertension, with one of the many complications being hypertensive retinopathy. In one study, the prevalence of retinopathy was found to be 85% amongst those with severe hypertension, and 25% for those with mild hypertension. Retinal consequences of hypertension include arteriolar narrowing, hemorrhages, cotton wool spots (localized hypoxia), and optic disk swelling. Other retinal changes include hyalinization of arteriolar walls, thickening of the vascular basement membrane, closure of capillaries, smooth muscle degeneration, and blood-retinal barrier dysfunction. Additionally, hypertension is a major risk factor for the highly threatening events of retinal artery or vein occlusion. The primary treatment for hypertensive retinopathy is to reduce blood pressure; however, consequences of the disease including narrowing of arterioles persist even following anti-hypertension medication. Therefore, a better knowledge of the mechanisms of the disease could lead to the development of additional and more effective therapeutic options. Our overall hypothesis is that the vascular complications of hypertensive retinopathy are due phenotypic changes in endothelial and smooth muscle cells, with vessel wall remodeling limiting recovery even with anti-hypertensive medication. The specific aims are to: (1) determine the sex-dependent expression of the glycocalyx in the retina, and determine the consequences of hypertension on this expression, (2) examine the sex-dependent expression of platelet endothelial adhesion molecule-1 and vascular endothelial cadherin in the retina, and test the hypothesis that changes in these junctional molecules in the hypertensive retina are due to endothelial-to- mesenchymal transition, and (3) test the hypothesis that remodeling of blood vessel walls in the SHR retina induces susceptibility to poor retinal perfusion when high blood pressure is reduced to normal.

Key facts

NIH application ID
10367158
Project number
1R01EY032509-01A1
Recipient
LOUISIANA STATE UNIV HSC SHREVEPORT
Principal Investigator
NORMAN R HARRIS
Activity code
R01
Funding institute
NIH
Fiscal year
2022
Award amount
$365,000
Award type
1
Project period
2022-09-30 → 2026-06-30