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Yang Liu, Jinzi Wu, Liang-jun Yan, Abbot F. Clark; High glucose impairs optic nerve head astrocyte phagocytosis prior to retinal ganglion cell degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3549. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell (RGC) degeneration is an early event in the pathogenesis of diabetic retinopathy. The astrocytes in the myelination transition zone (MTZ) of the optic nerve head (ONH) play important role in maintaining RGC homeostasis by engulfing axonal mitochondria. In this study, we evaluated the effects of high glucose on phagocytic activities of ONH astrocytes.
Primary mouse MTZ astrocytes were cultured in defined astrocyte medium containing 5.5 or 25 mM D-glucose (representing normal and high glucose conditions, respectively). Astrocytes were also treated with 5.5 mM D-glucose plus 19.5 mM L-glucose and 25 mM D-manntol as osmolality controls. Phagocytic activity of astrocytes were determined by flow cytometry-based phagocytosis assay 4 weeks after treatment. Eyes from TallyHo/Jng and streptozotocin-induced diabetic mice were collected 4 weeks after development of diabetes. Cryosections were immunostained with specific antibodies against glial fibrillary acidic protein (GFAP), Mac-2 and RNA binding protein with multiple splicing (RBPMS). Pattern electroretinogram (PERG) was also performed to determine RGC function.
Compared to other culture conditions, astrocytes cultured in medium containing 25 mM glucose showed significantly decreased (59.1 ± 5.1 % of 5.5 mM glucose group) percentage of cells with phagosomes. Consistent with the results obtained from in vitro experiments, diabetic mice showed decreased GFAP and Mac-2 expression at the MTZ compared to age-matched control mice. Retinal sections labeled with RBPMS demonstrated similar RGC numbers between diabetic and control mice. As expected, there was no significant difference in PERG responses between diabetic and control mice.
High glucose impairs optic nerve head astrocyte phagocytosis prior to retinal ganglion cell degeneration, which may initiate diabetic neurodegeneration. Our study provides a new insight into pathogenesis of diabetic retinopathy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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