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Alfred Yu, Luca Della Santina, Yvonne Ou; The role of microglia in the mechanism of retinal circuit disassembly in a mouse model of ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2013. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma, the leading cause of irreversible blindness worldwide, is a group of diseases in which the final common pathway is retinal ganglion cell (RGC) death. Recent evidence in a mouse model of laser-induced ocular hypertension (LIOH) suggests that among αRGCs, αOFF-transient RGCs are particularly vulnerable to injury and that the degree of presynaptic ribbon density loss is greater in the OFF sublamina of the inner plexiform layer (IPL) (Ou et al., JNeuroSci 2016). To better understand the mechanism of how neurons stratifying in the IPL are disassembled, we examined microglia in the IPL of retinas from LIOH and naïve animals. We hypothesized that there would be a greater increase in microglia density and activation in the OFF sublamina of the IPL that is contributing to the pruning of OFF synapses in diseased retina.
Laser photocoagulation of the limbal and episcleral veins was performed on one eye of CD-1 mice, which produced a transient elevation of IOP lasting one week. Retinal whole-mounts were isolated from mice 7 days post-LIOH and naïve control mice. Retinas were then immunolabeled with Iba1 to identify microglia. The IPL was divided in half to perform 3D analysis of microglia (volume and distribution along IPL strata) in the OFF and ON sublamina of the IPL.
Total volume of Iba1-positive microglia significantly increased in the OFF and ON sublamina compared to control (control vs LIOH, OFF: 17,642.69 μm3 vs 42,161.83 μm3 p=0.001; ON: 6,779.13 μm3 vs 15,671.83 μm3 p=0.01, in a total volume of approximately 0.008 mm3). At each stratification level (0% = inner nuclear layer (INL); 100% = ganglion cell layer (GCL)) the absolute volume of microglia in the LIOH vs control IPL increased significantly. The maximum volume of Iba1 shifted from the outer bounds of the IPL towards the center (control vs LIOH, OFF: 3.73% vs 12.25 % p=0.23; ON: 88.85% vs 73.50% p=0.06).
Transient ocular hypertension leads to an increase in Iba1 volume throughout the IPL. In control retinas microglia density is greater in the OFF sublamina and is localized to layers closest to the INL and GCL. After LIOH, microglia migrate towards the central region of the IPL. The preferential loss of αOFF-transient RGCs may be due to a greater density and localization of microglia in the OFF sublamina and their migration towards the central region of the IPL after injury.
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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