# Microglia-Vascular Interaction in Alteration of Blood-Retinal Barrier in Diabetic Retinopathy

> **NIH VA I01** · ALBUQUERQUE VA MEDICAL CENTER · 2022 · —

## Abstract

Significance: Diabetes is a global epidemic with 48 million people affected in USA, and the prevalence is
expected to increase to 63 million by 2045. The disease represents a significant public health problem. Diabetes
within the Veterans Health Administration (VHA) poses a significant challenge because the estimated
prevalence of diabetes among its enrolled patients is as high as 25%, substantially higher than the general
population. Diabetes is the third most common VHA diagnosis and accounted for 25% of pharmacy costs and
over 1.7 million hospital bed days. Diabetic retinopathy, a microvascular complication of diabetes is the leading
cause of vision loss in middle-aged adults. Despite the use of therapeutics targeting the vascular endothelial
growth factor (VEGF), about two thirds of patients do not recover vision, and the effect is transient, needing
repeated intravitreal injections of drugs. Rationale: Chronic inflammation in retina plays a major role in BRB
alteration resulting in vascular leakage. Our preliminary work presents novel evidence that there is increased
influx of monocytes and activation of microglia in the retina in diabetes. The goal of this research proposal is to
determine what factors are secreted by the activated microglia and how those factors interact with vascular
cells leading to alteration of the BRB. Hypothesis: Activated microglia in the diabetic retina secrete
factors that affect pericyte-endothelial interactions leading to BRB alteration. Aims: 1)
Determine effect of microglia depletion on the retinal vasculature and structure in the context of diabetic
retinopathy, 2a) Identify and prioritize “candidate genes” by analyzing the core transcriptional signatures of
activated retinal microglia in an animal model of diabetes in relationship to blood-retinal barrier alteration.
2b) Validate the role of “microglial candidate genes” on endothelial cell permeability and blood retinal
barrier alteration in diabetes and 3) Test the druggability of the functionally validated candidate genes
using an off-patent small molecule library in cell culture models and a diabetic animal model. Design: In
this research proposal, next generation sequence (NGS) technology will be utilized to investigate the molecular
basis of alteration of the BRB in diabetes. This research will address a critical scientific gap by identifying
molecular mediators beyond VEGF that alter the BRB. Relevance: The findings may help in development of
novel biomarkers and improved therapeutic strategies targeting these molecules in both type 1 and 2 diabetes
patients that may prevent vision loss in those who poorly respond to anti-VEGF drugs. Our approach is
innovative because this proposal introduces an innovative strategy that targets the mechanisms of stabilizing
the initial step of microglia dysfunction in diabetes, a critical upstream event for the development of diabetic
macular edema.

## Key facts

- **NIH application ID:** 10258513
- **Project number:** 1I01BX005348-01A1
- **Recipient organization:** ALBUQUERQUE VA MEDICAL CENTER
- **Principal Investigator:** ARUP DAS
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10258513

## Citation

> US National Institutes of Health, RePORTER application 10258513, Microglia-Vascular Interaction in Alteration of Blood-Retinal Barrier in Diabetic Retinopathy (1I01BX005348-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10258513. Licensed CC0.

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