Vascular Control in Diabetic Retinopathy
April 1, 2016 to March 31, 2021
National Institutes of Health (NIH)
National Eye Institute (NEI)
Aim 1, we will test the hypothesis that decline in vasomotor ability of pericytes and changes in their gap junction coupling mediate impaired vasomotor control in diabetic retina.
- 1a) we will measure pericyte activity in response to electrical and chemical stimulation
- 1b) we will determine whether decreased gap junction coupling reduces pericyte activity propagation. This is relevant, since individual pericytes control local capillary diameter, while signaling between pericytes via gap junctions allows for the spatial distribution of vasomotor control.
Aim 2, we will test the hypothesis that reduced vascular sensitivity to cholinergic signaling and a decline in cholinergic amacrine cell function both impair vasomotor activity.
- 2a) we will use cholinergic agonists and antagonists to determine whether the efficacy of cholinergic regulation of capillary diameter is compromised in diabetic retina.
- 2b) we will use an optogenetic approach to directly activate cholinergic amacrine cells, to determine whether they are functionally compromised. Altered retinal blood flow is a common characteristic of patients with early stages of diabetic retinopathy, and likely contributes to latr complications of the disease. Functional compromises to the cells responsible for regulating blood flow in the retina may account for this vasomotor deficit. Understanding the mechanisms of vasomotor dysfunction could reveal novel therapeutic targets, and provide additional approaches for treating diabetic retinopathy.
Visual Plasticity and Repair Laboratory