Walling off or ‘bunkering’ retina can save eyesight, suggests study

Connecticut [US], March 8 (ANI): The retina is a layer of photoreceptors cells and glial cells within the eye that captures incoming photons and transmits them along neuronal pathways as both electrical and chemical signals for the brain to perceive a visual picture. Chronically stressing the retina can weaken it and damage our ability to see. But retinal cells have a remarkable ability to wall off damage. This was discovered by a team of neuroscientists led by UConn Health.
The study was published in ‘Proceedings of the National Academy of Sciences’ (PNAS).
The walling-off or “bunkering” of the damage may be key to preserving our eyesight.
Muller glia are very long cells that span the thickness of the retina and provide mechanical strength, supporting the neurons and light receptors that detect light, shape and colour.
Muller glia are also involved in protein changes related to retinal injury, being the first cells to respond. UConn School of Medicine neuroscientist Royce Mohan and colleagues discovered that the endfeet, a specialized zone in Muller cells, is where proteins become modified when the retina is under stress. These end feet are at the opposite end of the retina, quite a distance from light receptors. The researchers propose in the paper that this segregation of the endfeet and light receptors may permit light detection to continue even as the retina responds to stress.
The modification of proteins that Mohan’s lab has been studying is called citrullination. In citrullination, the amino acid arginine is changed into citrulline. Because in the early stages of stress or disease, the citrullinated proteins stay sequestered in the Muller cells’ endfeet, Mohan called this area the citrullination bunker. But if this bunker is chronically engaged, then the overabundance of citrullinated proteins reach other parts of the retina. Muller cells in human age-related macular degeneration (AMD) and mouse models of retinal degeneration reveal citrullinated proteins extending out of the endfeet and spreading throughout the cells.
Citrullination may have many effects on Muller glial cells which are only just being understood. For example, arginine is positively charged, while citrulline is not. The loss of the positive charges is permanent, and may irreversibly change the flexibility or other mechanical properties of the Muller glial cells. This may cause the Muller cells to become incapable of adapting to fluid build-up when the retina swells up under stress. Alternatively, it’s possible the citrullinated proteins could appear foreign to the body and draw the attention of the immune system, potentially beginning autoimmune disease. Turning off citrullination in the end feet bunker could delay or avoid these problems and preserve eyesight for longer.
This team has also identified that the endfeet citrullination process is controlled by an enzyme known as peptidyl arginine deiminase-4 (PAD4). Small molecule inhibitors of PAD4 have been developed for other types of citrullination-dependent diseases, such as rheumatoid arthritis. Mohan believes that such therapeutic agents could be applied to reduce citrullination at the early stages of AMD and spare the retina of undesired responses to this protein modification. (ANI)