Retinal microglia implicated in disease progression.
The results of a study from the National Eye Institute in Bethesda (USA), published in EMBO Molecular Medicine, show that retinal microglia contribute to the loss of rods in retinitis pigmentosa, an inherited retinal disease that leads to blindness and for which there is currently no effective treatment.
In retinitis pigmentosa the rods degenerate as a result of genetic mutations, but unfortunately there are more than 100 genes that appear to be involved in this degenerative process. This implies that gene therapy, however promising, remains a distant and in many cases unattainable mirage.
The results of the study on retinal microglia are important because they identify a potential target for new therapeutic approaches that could postpone the death of visual receptors and the associated loss of vision.
Microglia - a collection of glial cells that function as macrophages in the central nervous system - constitute an endogenous defence of the brain and immune system. Microglial migration is essential in immune reactions, wound healing and microglial phagocytosis plays a central role in the removal of apoptotic cells. Indeed, in response to neurological injury, microglia accumulate at the site of damage and remove cell debris and even part of the damaged cells.
Researchers at the National Eye Institute in Bethesda, led by Wai T. Wong, studied the interaction between retinal macroglia and photoreceptors to identify the nature of cellular mechanisms involved in neurodegenerative processes. The study started with mice that had a mutation in the Pde6b gene, recognised as one of the causes of retinitis pigmentosa in humans.
In retinitis pigmentosa, this gene mutation induces cellular stress in the rods and causes the production of phosphatidylserine, which acts as a signal (called 'eat me') capable of turning the rods into a target for phagocytosis by microglia. The destruction takes place through a dynamic process of contact and engulfment, which was also documented with a video.
Microglial phagocytosis could be blocked by molecular inhibition, resulting in improved morphological and functional parameters of degeneration.
These results raise hopes for new therapies targeting retinal microglia that can slow down irreversible visual loss in patients with retinitis pigmentosa.
For more details see thefull article in EMBO Molecular Medicine
Dr. Carmelo Chines
Direttore responsabile
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