# Retinal Muller Glial Cells in the initiation of diabetic retinopathy

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $376,794

## Abstract

PROJECT SUMMARY/ABSTRACT
The molecular mechanisms responsible for the initiation of diabetic retinopathy (DR), and the primary cellular
targets of diabetes in the retina have not been fully elucidated. This represents a significant barrier to the
development of effective therapies to prevent or slow down the initiation of the disease. When challenged by
diabetes, retinal neurons, glia, and the vasculature all display abnormalities. Even though it is currently not
clear which cell types are the primary targets of diabetes, Müller glial cells (MG), as one of the first responders
of diabetes in the retina, are essential for the development of diabetic retinopathy. However, the molecular
mechanisms controlling the diabetes-induced Müller glial responses remain understudied.
 We applied single cell transcriptomic analysis (single cell RNA-seq) to systematically profile diabetes-
induced multicellular responses in the retina of diabetic rat models (preliminary studies). Among the 53 types of
retinal cell detected by single cell RNA-seq, MG were one of the first responders to diabetes at the
transcriptional level. Notably, MG initially upregulated genes that play protective roles in other systems,
including anti-apoptosis, anti-proliferation, anti-oxidation, and anti-inflammation genes, but failed to maintain
expression levels of these protective genes as the disease progressed. This failure could contribute to the
development of DR. We hypothesize that MG exert protective roles by upregulating protective genes in the
early stage of DR, and that enhancing this intrinsic protective mechanism will protect the retina from diabetes-
induced damage.
 The proposed studies will test this hypothesis in two aims. In Aim 1, we will focus on studying one of the
candidate protective genes, Zinc finger protein 36 homolog (Zfp36), which was initially upregulated by diabetes
in MG and then downregulated as DR progressed, using diabetic rat models. In Aim 2, we will determine
whether multiplexing activation of protective pathways in MG with a novel CRISPR-based technique can
further protect the retina from diabetes-induced damage.
 In summary, the proposed study aims to uncover the roles of MG in initiating DR, focusing on dissecting
their protective effects. This work will lead to better understanding of DR and new therapeutic candidates.

## Key facts

- **NIH application ID:** 10873956
- **Project number:** 5R01EY033792-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sui Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,794
- **Award type:** 5
- **Project period:** 2022-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873956

## Citation

> US National Institutes of Health, RePORTER application 10873956, Retinal Muller Glial Cells in the initiation of diabetic retinopathy (5R01EY033792-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10873956. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*