Abstract
Purpose :
Mitochondrial dysfunction is a potential mechanism contributing to the pathogenesis of diabetic retinopathy (DR) and is implicated in the cell death of various retinal cell types, including photoreceptor cells, Müller cells, endothelial cells, and pericytes, under simulated hyperglycemia. Changes in mitochondrial membrane structure in the microvasculature and expression of mitochondria-related genes have also been reported in the retina of diabetic rats and patients. However, how diabetes affects mitochondrial function in intact retinal tissue is not well understood. This study aimed to investigate the diabetes-induced changes in retinal morphology and mitochondrial bioenergetics during the early time course of diabetes with C57BLKsJ-db/db (db/db) mice.
Methods :
Male db/db mice (n=5) with fasting blood glucose levels ≥ 13.9 mmol/L were used in this study, and their normoglycemic heterozygous littermates (db/+, n=7) were regarded as the control group. The mice were sacrificed at 25-week-old, when their retinas were harvested for assessing changes in retinal morphology and ex vivo mitochondrial bioenergetics by using immunohistochemistry and the Seahorse XFe24 analyzer, respectively.
Results :
Compared to db/+ mice, the retina of the db/db mice at 25-week of age was thinner at the outer (p<0.01, unpaired t-test) and inner nuclear layers (p<0.001), with lower photoreceptor (p<0.05) and cone cell density (p<0.01). Immunohistochemistry also indicated a higher level of Müller cell activation in the retinas of db/db than db/+ mice (p<0.05). Seahorse assays revealed that the retinas of db/db mice had lower basal (p<0.01) and maximal respiration (p<0.05), indicating weaker mitochondrial functions than the db/+ mice. In addition, the matrix metallopeptidase 9 (MMP-9) activation was stronger in the retinas of db/db mice than the db/+ mice (p<0.01).
Conclusions :
Our result showed that diabetes-induced neurodegeneration of db/db mice retina was accompanied by a declined mitochondrial function and an increased level of MMP-9 activation.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.