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Erythropoietin Protects Retinal Cells in Diabetic Rats Through Upregulating ZnT8 via Activating ERK Pathway and
Guoxu Xu1, Daohuan Kang2, Chaoyang Zhang3
1Department of Ophthalmology of Shanghai Tenth People's Hospital Tongji Eye Institute, Tongji University School of Medicine (TUSM), Shanghai, China 2Department of Ophthalmology, Second Affiliated Hospital of Soochow University, Suzhou, China.
Investigative Ophthalmology & Visual Science
|January 1, 2016
Summary
Erythropoietin (EPO) helps maintain zinc balance in diabetic rat retinas by increasing Zinc transporter 8 (ZnT8) expression. This protective mechanism involves activating the ERK pathway and reducing hypoxia-inducible factor-1α (HIF-1α).
Area of Science:
- Ophthalmology
- Cell Biology
- Endocrinology
Background:
- Diabetic retinopathy is a leading cause of vision loss.
- Zinc transporter 8 (ZnT8) plays a role in retinal function and is downregulated in hypoxic conditions.
- Hypoxia-inducible factor-1α (HIF-1α) is implicated in diabetic retinopathy pathogenesis.
Purpose of the Study:
- To investigate the effect of erythropoietin (EPO) on ZnT8 expression and retinal cell protection in diabetic rats.
- To elucidate the underlying mechanisms involving HIF-1α and the ERK pathway.
Main Methods:
- Diabetes was induced in Sprague-Dawley rats, followed by intravitreal EPO injection.
- Rat Müller cells (rMC-1) were treated with EPO under hypoxic conditions (CoCl2).
- Cell viability, death, intracellular zinc, and expression of ZnT8, HIF-1α, AKT, and ERK were assessed.
Main Results:
- EPO treatment in diabetic rats decreased HIF-1α and increased ZnT8 expression.
- In hypoxic rMC-1 cells, EPO enhanced viability, reduced intracellular zinc, activated ERK, downregulated HIF-1α, and upregulated ZnT8.
- EPO's effects were mediated via the ERK pathway and blocked by sEPOR and U0126.
Conclusions:
- EPO protects diabetic retinas by activating the ERK pathway, downregulating HIF-1α, and upregulating ZnT8, thereby maintaining zinc homeostasis.
- This study identifies a novel protective mechanism for EPO and suggests a potential therapeutic target for diabetic retinopathy.
