Related Experiment Video
Updated: Jul 16, 2026
Alternate Immersion in Glucose to Produce Prolonged Hyperglycemia in Zebrafish
Published on: May 5, 2021
Induction of a Müller Glial Cell-Specific Protective Pathway Safeguards the Retina From Diabetes-Induced Damage
Cheng-Hui Lin1, Man-Ru Wu1, Bogdan Tanasa1
1Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA.
Abstract:
Diabetes can lead to cell type-specific responses in the retina, including vascular lesions, glial dysfunction, and neurodegeneration, all of which contribute to retinopathy. However, the molecular mechanisms underlying these cell type-specific responses, and the cell types that are sensitive to diabetes have not been fully elucidated. Using single-cell transcriptomics, we profiled the transcriptional changes induced by diabetes in different retinal cell types in rat models as the disease progressed. Rod photoreceptors, a subtype of amacrine interneurons, and Müller glial cells (MGs) exhibited rapid responses to diabetes at the transcript levels. Genes associated with ion regulation were upregulated in all three cell types, suggesting a common response to diabetes. Furthermore, focused studies revealed that although MG initially increased the expression of genes playing protective roles, they cannot sustain this beneficial effect. We explored one of the candidate protective genes, Zinc finger protein 36 homolog (Zfp36), and observed that depleting Zfp36 in rat MGs in vivo using adeno-associated virus-based tools exacerbated diabetes-induced phenotypes, including glial reactivation, neurodegeneration, and vascular defects. Overexpression of Zfp36 slowed the development of these phenotypes. This work unveiled retinal cell types that are sensitive to diabetes and demonstrated that MGs can mount protective responses through Zfp36.
Insights
Diabetes impacts specific retinal cells, like Müller glial cells (MGs), which initially show protective gene expression but cannot sustain it. The gene Zfp36 plays a key role in mitigating diabetes-induced retinal damage.
Area of Science:
- Ophthalmology
- Molecular Biology
- Diabetic Retinopathy Research
Background:
- Diabetes causes cell-specific retinal damage, including vascular lesions, glial dysfunction, and neurodegeneration, contributing to retinopathy.
- The precise molecular mechanisms and susceptible cell types in diabetic retinopathy remain incompletely understood.
Purpose of the Study:
- To identify diabetes-sensitive retinal cell types and elucidate the molecular mechanisms of diabetic retinopathy.
- To investigate the role of Müller glial cells (MGs) and specific protective genes in mitigating diabetic damage.
Main Methods:
- Single-cell transcriptomics was employed to profile transcriptional changes in rat retinal cells during diabetes progression.
- Functional studies using adeno-associated virus (AAV) tools were performed to manipulate Zinc finger protein 36 homolog (Zfp36) expression in MGs.
Main Results:
- Rod photoreceptors, amacrine interneurons, and Müller glial cells (MGs) showed rapid transcriptional responses to diabetes.
- Upregulation of ion-regulation genes was observed across these cell types, indicating a common diabetic response.
- MGs initially upregulated protective genes but could not sustain this effect; Zfp36 depletion exacerbated diabetic phenotypes, while its overexpression conferred protection.
Conclusions:
- This study identifies key retinal cell types sensitive to diabetes, including MGs, rod photoreceptors, and amacrine cells.
- Müller glial cells (MGs) can initiate protective responses against diabetes-induced retinal damage, mediated in part by Zfp36.
- Zfp36 emerges as a critical factor in protecting against diabetic retinopathy progression.
