دورية أكاديمية

Microglia preserve visual function loss in the aging retina by supporting retinal pigment epithelial health.

التفاصيل البيبلوغرافية
العنوان: Microglia preserve visual function loss in the aging retina by supporting retinal pigment epithelial health.
المؤلفون: Karg, Margarete M., Moorefield, May, Hoffmann, Emma, Philipose, Hannah, Krasniqi, Drenushe, Hoppe, Cindy, Shu, Daisy Y., Shirahama, Shintaro, Ksander, Bruce R., Saint-Geniez, Magali
المصدر: Immunity & Ageing; 10/14/2023, Vol. 20 Issue 1, p1-14, 14p
مصطلحات موضوعية: VISION, RHODOPSIN, MACULAR degeneration, MELANOPSIN, MACROPHAGE colony-stimulating factor, RETINA, RETINAL injuries
مستخلص: Background: Increased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding the changes that occur in the eye due to aging is important in enhancing our understanding of AMD pathogenesis and the development of novel AMD therapies. Microglia, the resident brain and retinal immune cells are associated with both maintaining homeostasis and protection of neurons and loss of microglia homeostasis could be a significant player in age related neurodegeneration. One important characteristic of retinal aging is the migration of microglia from the inner to outer retina where they reside in the subretinal space (SRS) in contact with the retinal pigment epithelial (RPE) cells. The role of aged subretinal microglia is unknown. Here, we depleted microglia in aged C57/BL6 mice fed for 6 weeks with a chow containing PLX5622, a small molecule inhibitor of colony-stimulating factor-1 receptor (Csf1r) required for microglial survival. Results: The subretinal P2RY12 + microglia in aged mice displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets reminiscent of lipofuscin. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, one of the main functions of retinal pigmented epithelial cells. PLX5622 treatment depleted up to 90% of the retinal microglia and was associated with significant loss in visual function. Mice on the microglia depletion diet showed reduced contrast sensitivity and significantly lower electroretinogram for the c-wave, a measurement of RPE functionality, compared to age-matched controls. The loss of c-wave coincided with a loss of RPE cells and increased RPE swelling in the absence of microglia. Conclusions: We conclude that microglia preserve visual function in aged mice and support RPE cell function, by phagocytosing shed photoreceptor outer segments and lipids, therefore compensating for the known age-related decline of RPE phagocytosis. [ABSTRACT FROM AUTHOR]
Copyright of Immunity & Ageing is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
قاعدة البيانات: Complementary Index
الوصف
تدمد:17424933
DOI:10.1186/s12979-023-00358-4