1. Systemic C-peptide supplementation ameliorates retinal neurodegeneration by inhibiting VEGF-induced pathological events in diabetes.
- Author
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Lee AJ, Moon CH, Lee YJ, Jeon HY, Park WS, and Ha KS
- Subjects
- Animals, Mice, Vascular Endothelial Growth Factor A metabolism, C-Peptide metabolism, Reactive Oxygen Species metabolism, Retina metabolism, Vascular Endothelial Growth Factors, Dietary Supplements, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental metabolism, Diabetic Retinopathy metabolism, Hyperglycemia metabolism
- Abstract
Diabetic retinopathy (DR) is caused by retinal vascular dysfunction and neurodegeneration. Intraocular delivery of C-peptide has been shown to be beneficial against hyperglycemia-induced microvascular leakage in the retina of diabetes; however, the effect of C-peptide on diabetes-induced retinal neurodegeneration remains unknown. Moreover, extraocular C-peptide replacement therapy against DR to avoid various adverse effects caused by intravitreal injections has not been studied. Here, we demonstrate that systemic C-peptide supplementation using osmotic pumps or biopolymer-conjugated C-peptide hydrogels ameliorates neurodegeneration by inhibiting vascular endothelial growth factor-induced pathological events, but not hyperglycemia-induced vascular endothelial growth factor expression, in the retinas of diabetic mice. C-peptide inhibited hyperglycemia-induced activation of macroglial and microglial cells, downregulation of glutamate aspartate transporter 1 expression, neuronal apoptosis, and histopathological changes by a mechanism involving reactive oxygen species generation in the retinas of diabetic mice, but transglutaminase 2, which is involved in retinal vascular leakage, is not associated with these pathological events. Overall, our findings suggest that systemic C-peptide supplementation alleviates hyperglycemia-induced retinal neurodegeneration by inhibiting a pathological mechanism, involving reactive oxygen species, but not transglutaminase 2, in diabetes., (© 2023 Federation of American Societies for Experimental Biology.)
- Published
- 2023
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