Abstract
Purpose :
Retinitis pigmentosa is a group of inherited blinding disorders affecting 1 in 4000 people worldwide. In these disorders, phagocytic clearance of dead photoreceptor cell bodies is crucial for preventing additional retinal damage due to accumulation of cellular debris. The purpose of this study was to identify and characterize the cells responsible for the clearance of dead photoreceptor cells in a mouse model of retinitis pigmentosa.
Methods :
Taking advantage of a mouse model of retinitis pigmentosa (RhoP23H/P23H), we clarified the roles of Müller glia in the phagocytosis of rod photoreceptor cells. To analyze the phagocytic events, we designed a novel method to study phagosomes and phagolysosomes in individual and dissociated Müller glial cells. To visualize phagocytic events in fixed retinas, we took advantage of contemporary TEM and fluorescence microscopy techniques. These studies allowed us to document the major role of Müller glial cells as well as the supportive role of macrophages in phagocytosing and clearing rod photoreceptor cells at an early stage of retinal degeneration.
Results :
During an early stage of retinal degeneration in RhoP23H/P23H mice, nearly 50 % of Müller glial cells engaged in phagocytosis of dead or dying rod photoreceptors. In these cells, more than 90 % of phagosomes matured into phagolysosomes. These results indicate that Müller glial cells are the primary phagocyte. In contrast, macrophages migrated to the inner part of the outer nuclear layer during this stage of retinal degeneration, participating in the phagocytosis of a limited population of dying or dead photoreceptor cells. During the development of healthy retinas in wild type mice, Müller glial cells phagocytosed cell bodies of photoreceptor and other retinal neurons which died as part of ontogenetic cell death.
Conclusions :
The phagocytic function of Müller glia is responsible for retina homeostasis and reorganization under normal and pathological conditions.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.