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Abram Akopian, Sandeep Kumar, Hari Ramakrishnan, Suresh Viswanathan, Stewart A Bloomfield; Ablation of neuronal gap junctions prevents the changes in bipolar cell structure and function seen in a mouse model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2569. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We studied the structural and functional changes of retinal bipolar cells (BCs) in a mouse model of glaucoma. We also determined whether ablation of gap junctions (GJs), which we showed last year at ARVO can protect inner retinal neurons, can also prevent BC changes in glaucomatous retinas.
Experimental glaucoma was induced in adult C57BL/6 (WT) and Cx36 KO mice by intracameral injection of polystyrene microbeads. The rod (R) BCs were labeled with anti- PKCα, while anti-Chx10 stained all BC nuclei. ERG recordings were performed under both scotopic and photopic conditions. Statistical significance was determined using Student’s t-test.
At 4 weeks after initial bead injection of WT mouse eyes, the number of RBCs was reduced by 19% (p<0.05) as compared to control values, whereas the number of cone (C) BCs remained unchanged. At 8 weeks after bead injection, the RBC count was reduced further to 31% (p<0.001) and the number of CBCs was reduced by 27% (p<0.001). The RBCs in glaucomatous eyes showed reduced dendritic branching with many nearly devoid of dendrites. The PKCα-positive axon terminals in the IPL were markedly reduced in size with fewer varicosities than seen in control retinas. The density of CtBP2-positive ribbon synapses was significantly reduced (p<0.01) in the OPL of bead-injected retinas. They appeared as large patches often not associated with BC dendrites, which contrasted with the horseshoe structures terminating near BC dendrites seen in control retinas. ERGs measured 8 weeks after bead injection showed scotopic and photopic b-waves whose amplitudes were significantly reduced (p<0.05) relative to control values. To examine whether GJ ablation protected BCs, we induced glaucoma in Cx36 KO mice. We found no significant change in the number of BC somata or in their dendritic or axonal architecture in glaucomatous retinas of KO mice. Consistent with these findings, the b-wave of the ERG in these animals was similar to that recorded under control conditions (p>0.5).
The structure and function of BCs are significantly altered in a mouse model of glaucoma. As seen for inner retinal neurons, ablation of GJs protected both the structural and functional integrity of BCs. Since most BCs do not express GJs, these results suggest that the harmful effects of glaucoma on BCs are secondary to those reported for inner retinal neurons.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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