Cells within retinal vessels can acquire resistance against hyperglycaemia, protecting patients against diabetic retinopathy, according to new research.
Around one-third of patients with diabetes mellitus develop diabetic retinopathy, which is a leading cause of blindness in working-age individuals. Diabetic retinopathy usually develops after many years of diabetes mellitus, and many patients do not develop diabetic retinopathy for more than 50 years.
New research has suggested that the endogenous system responsible for protecting human retinal endothelial cells from the harmful effects of hyperglycaemia may also be responsible for the delayed onset of diabetic retinopathy.
In addition to this, the degradation of the endogenous system may create an environment for the development of diabetic retinopathy.
The study has been published in The American Journal of Pathology.
The complications of diabetes mellitus
“The prevailing understanding of what causes diabetic retinopathy predicts that it will develop soon after the onset of diabetes mellitus,” explained Andrius Kazlauskas from the Department of Ophthalmology and Visual Sciences and Physiology and Biophysicy at the University of Illinois, Chicago.
“Yet this is not the case. Although the long delay from the onset of diabetes mellitus to the development of Diabetic retinopathy is a well-known clinical phenomenon, there is relatively little effort to investigate the underlying reason for this delay. Uncovering this information constitutes an exciting opportunity to improve current approaches to prevent diabetes mellitus from progressing to diabetic retinopathy.”
Exposing vascular endothelial cells to high levels of glucose is common in in vitro models of diabetic retinopathy. The researchers exposed human retinal endothelial cells to normal glucose and high models. The research team were surprised to find that prolonged exposure to high glucose was beneficial and not detrimental, as they expected.
After one day of exposure, the health of the cells declined, however, as the duration of exposure continued, the cells recovered and became resistant to diabetes mellitus-related damage.
The researchers also observed an association between glucose exposure and improved mitochondria functionality.
The process in which cells remove damaged mitochondria is known as Mitophagy. Disruption of this quality control system has been associated with many diseases. Despite an initial negative impact, exposure to glucose eventually improved mitochondrial functionality, with increased clearance of damaged mitochondria after ten days. These results suggest that mitochondrial dynamics can compromise cells’ ability to endure high glucose.
HIMA may protect against diabetic retinopathy
“The compelling role of mitochondrial dysfunction in the development of diabetic retinopathy supports our central concept of a hyperglycemia-induced mitochondrial adaptation (HIMA) system, the purpose of which is to preserve the functionality of mitochondria. We posit that the loss of HIMA sets the stage for advancing to diabetic retinopathy,” explained Dr Kazlauskas
The HIMA concept can improve subsets of retinal cells, which is highly beneficial in beneficial for the whole retina. Existing research has found that even small reductions in the degree or type of insult to the retina can protect animals that have from developing diabetic retinopathy. These findings suggest that the development of diabetic retinopathy may involve a small shift in the balance between exogenous insults and endogenous systems.
“Does HIMA exist in vivo, does it protect patients from diabetic retinopathy, and is its demise a prerequisite for progression? Our ongoing research is focused on answering these open questions,” concluded Dr Kazlauskas.
