Friday, April 26, 2024
4/26/2024
Project Summary One of the defining features of blood circulation in the central nervous system is its capacity to be regulated by signaling from neurons and glia. In the retina, this feature, termed neurovascular coupling (NVC), occurs on the level of larger arterioles down to individual capillaries. Dilation and constriction of these capillaries is controlled by vasoactive cells called pericytes. The retinal vasculature is organized in an expansive network of three laminae which supply nutrients to distinct types of neurons organized in corresponding layers. Previous work has shown that flow through each lamina is differentially regulated by light, but the mechanisms of NVC in the retina and how they could differ between laminae remain poorly understood. Revealing the mechanisms of NVC in the retina is an important public health concern because there is a growing body of evidence that NVC dysfunction is critical to the pathology of diabetic retinopathy, a blinding disease affecting 35% of patients with diabetes. Treatments for diabetic retinopathy are targeted towards late- stage vascular complications, but there are no current treatments targeted towards NVC dysfunction. This project seeks to determine the underlying parameters of light stimulus that lead to vasoactivity in the retina and the cellular mechanisms that make this possible. I will use electrophysiology and two-photon imaging to measure pericyte activity and capillary diameter in the ex vivo mouse retina, and I will develop a computational model of blood flow and nutrient diffusion throughout the retina. I will also explore the role of hyperglycemia in the NVC dysfunction seen in diabetes. Successful completion of this project will lead to a better understanding of how blood flow in the central nervous system is regulated, potential targets for therapy, and the establishment of a model system for future explorations of how the nervous and circulatory systems are intertwined.
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