About a third of patients with diabetes mellitus (DM) develop diabetic retinopathy (DR), one of the main causes of blindness in people of working age. DR usually develops after many years of diabetes, and some patients do not develop DR for over 50 years. New research suggests that an endogenous system that protects human retinal endothelial cells from the harmful effects of hyperglycemia (excess blood sugar) may be responsible for the delayed onset of DR. Moreover, the degradation of this protective system over time can pave the way for the development of DR. The new study appears in The American Journal of Pathologyedited by Elsevier.
“Current understanding of the causes of DR predicts that it will develop soon after the onset of DM,” explained lead researcher Andrius Kazlauskas, PhD, Departments of Ophthalmology and Visual Sciences and Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA. “Nevertheless, it is not the case. Although the long delay between the onset of DM and the development of DR is a well-known clinical phenomenon, there are relatively few efforts to investigate the underlying reason for this delay. Discovering this information is an exciting experience. possibility of improving current approaches to prevent DM from evolving into DR. »
Exposure of cultured cells, such as vascular endothelial cells, to elevated blood glucose is common practice. in vitro model of DR. The researchers cultured human retinal endothelial cells in media containing either normal or high glucose. Unexpectedly, they found that prolonged exposure to high blood sugar was beneficial and not detrimental. After one day, cell health declined, but as the exposure time was prolonged, the cells recovered and gained resistance to DM-related damage such as inflammation and death.
The researchers found that adaptation was associated with improved functionality of mitochondria. Mitophagy is the process by which cells eliminate damaged mitochondria, and disruption of this intrinsic quality control system is associated with many diseases. Although initially compromised, mitochondrial functionality was improved after 10 days of high glucose exposure, with increased clearance of damaged mitochondria. Interfering with mitochondrial dynamics compromised the cells’ ability to withstand high blood sugar. Cell death susceptibility increased and vascular endothelial growth factor responsiveness deteriorated.
Dr. Kazlauskas said these observations indicate the existence of an endogenous system that protects human retinal endothelial cells from the deleterious effects of hyperglycemia. “The central role of mitochondrial dysfunction in the development of DR supports our central concept of a hyperglycemia-induced mitochondrial adaptation (HIMA) system, the goal of which is to preserve mitochondrial functionality. We postulate that the loss of HIMA opens the way to move to DR.”
An important element of the HIMA concept is that improving the functionality of a subset of retinal cells will benefit the entire retina. Previous research has shown that even a small reduction in the degree or type of retinal insult can protect animals with DM from developing DR. Together, these findings suggest that the development of DR involves a relatively small shift in the balance between exogenous insults and endogenous systems that prevent DM-induced damage and drivers of pathogenesis.
Dr. Kazlauskas observed that the increasing incidence of DM, and therefore DR, worldwide exacerbates the need for effective approaches to protect patients from this serious complication. “Does HIMA exist Direct, protect patients from DR and is its disappearance a prerequisite for progression to DR? Our ongoing research aims to answer these open questions,” he concluded.
Source of the story:
Material provided by Elsevier. Note: Content may be edited for style and length.