About one third of patients with diabetes mellitus (DM) develop diabetic retinopathy (DR), a leading cause of blindness in working-age individuals. DR typically develops after many years of DM, and some patients do not develop DR for more than 50 years.
New research suggests that an endogenous system that protects human retinal endothelial cells from harmful effects of the hyperglycemia (an excess of blood sugar) may be responsible for the delayed onset of DR. Furthermore, degradation of this protective system over time may set the stage for development of DR. The new study appears in The American Journal of Pathology, published by Elsevier.
Exposing cultured cells, such as vascular endothelial cells, to high glucose is a common in vitro model of DR. The investigators cultured human retinal endothelial cells in either normal glucose or high glucose–containing media. Unexpectedly, they found that prolonged exposure to high glucose was beneficial, not detrimental. After one day, the health of the cells declined, but as the duration of exposure was prolonged, the cells recovered and acquired resistance to DM-related damage such as inflammation and death.
The investigators found that the adaptation was associated with improved mitochondria functionality. Mitophagy is the process in which cells remove damaged mitochondria, and disruption of this intrinsic quality control system is associated with many diseases. Though initially compromised, mitochondrial functionality was improved after 10 days of exposure to high glucose, with increased clearance of damaged mitochondria. Interfering with the mitochondrial dynamics compromised the cells’ ability to endure high glucose. Susceptibility to cell death increased, and responsiveness of vascular endothelial growth factor deteriorated.
