Abstract
Purpose :
Diabetic retinopathy (DR) is a common and specific neurovascular complication of diabetes. Dysregulation of amino acid metabolism has been showed to be involved in the pathogenesis of DR. Glutamine is the most abundant and versatile amino acid in human and many other mammals and extensively involved in various metabolic pathways. The present study was designed to investigate whether reprogramming amino acids metabolism by supplement of Ala-Gln, serving as a substitute for glutamine, plays protective roles on the diabetic retinopathy in streptozotocin (STZ)-induced rat model.
Methods :
Visual function of the rats was measured by electroretinogram (ERG). The expression of neurovascular markers and inflammation markers, such as glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were evaluated by western blot and immunofluorescence. The function of mitochondria was measured by immunostaining of TOM20. Regular body weight and blood glucose levels of rats were also monitored.
Results :
Amino acid sequencing indicated the ratio of glutamate/glutamine was upregulated in the retinas of STZ-induced rat compared to normal control. The activity of ERG was declined in STZ-induced diabetic rats, while the supplement of Ala-Gln increased ERG activities in the diabetic rats. In addition, pro-inflammatory factors VEGF and VCAM-1 were decreased in diabetic rats treated with Ala-Gln compared to those treated with vehicle. Further, the protein expressions of glutamine synthase, GFAP were decreased in Ala-Gln treated diabetic rats. Immunostaining of GFAP indicated less of Muller cells were activated in the retina of Ala-Gln treated diabetic rats. The glycolysis indicated by levels of PKM2, LDHA and LDHB were significant increased after Ala-Gln treatment. The mitochondrial TOM20 was upregulated in the retina of Ala-Gln treated diabetic rats.
Conclusions :
Our study has demonstrated that Ala-Gln has beneficial effects in diabetic retinopathy by improving the retinal neuronal function, reducing retinal glial activation and enhancing the glycolysis and the function of mitochondria in diabetic retinas. Therefore, reprograming metabolism by Ala-Gln may be a novel therapeutic avenue for retinal degeneration in DR.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.