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Yvonne Ou, Rebecca Jo, Luca Della Santina; Loss of OFF vs. ON bipolar cell axon terminals in an experimental model of glaucoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2019. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We previously demonstrated that ganglion cells with dendrites stratifying in the OFF sublamina of the inner plexiform layer (IPL) of the retina were more susceptible in a rodent model of experimental glaucoma (Ou et al., J Neurosci. 2016). We hypothesize that bipolar cells, the excitatory presynaptic partners of ganglion cells, might also be differentially susceptible to intraocular pressure (IOP) elevation depending on the level of stratification of their axon terminals within the IPL. The purpose of this study is to determine the effects of laser-induced ocular hypertension on various bipolar cell types at specific time points after IOP elevation.
IOP was elevated unilaterally using laser photocoagulation of the limbal and episcleral vessels of adult CD-1 mouse eyes. Whole-mount retina immunostaining with synaptotagmin-2 antibody was used to label both the type 2 OFF bipolar cell axon terminals and the type 6 ON bipolar cell axon terminals. The axon terminal volume occupancy was calculated for IPL volumes (n = 16) containing the various axon terminal types. The Student’s t-test was used to calculate statistical significance.
Given our finding of greater presynaptic ribbon loss in the OFF vs. ON sublamina of the IPL, we examined OFF and ON bipolar cell axon terminals. While after 7 days of IOP elevation there was no statistically significant difference in type 2 OFF vs. type 6 ON bipolar cell axon terminals, at 14 days there was a statistically significant decrease in axon volume occupancy of type 2 OFF bipolar cells (8.98% laser vs. 12% control; p < 0.02, 4 animals per group).
The finding of type 2 OFF bipolar cell axon terminal loss corroborates our hypothesis of OFF pathway vulnerability in experimental glaucoma. Uncovering the anatomic changes of ON vs. OFF bipolar cell types in response to IOP elevation may support strategies to probe specific light pathways in the diagnostic testing of glaucoma.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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