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Stewart A Bloomfield, Sandeep Kumar, Alexandra Benavente-Perez, Suresh Viswanathan, Abram Akopian; A novel model of experimental glaucoma in the marmoset. Invest. Ophthalmol. Vis. Sci. 2019;60(9):639.
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We reported previously that neuronal gap junctions form novel targets for neuroprotection in a mouse model of glaucoma (Akopian et al., 2017, JCI). To translate our results to a therapeutic treatment for glaucoma patients it is essential to first extend our results from rodents to non-human primates. The purpose of this study was to create an experimental glaucoma model in the common marmoset (Callithrix jacchus).
Intraocular pressure (IOP) was elevated by intracameral injections of 20-30 µL of a 10 µm polystyrene microbead suspension. Contralateral eyes served as controls. At 10 weeks after the microbead injection, retinal whole mounts and optic nerve cross sections from the lamina cribrosa region were analyzed histologically for cell loss as compared regionally to retinal controls. ERGs were recorded from eyes to determine any functional deficits.
To induce ocular hypertension in marmosets, we adopted and modified a microbead occlusion model to elevate IOP. Injection of microbeads resulted in a sustained elevation of IOP for at least 10 weeks from a mean value of 23.5 ± 1.0 mm Hg in normal eyes to 43.5 ± 3.5 mm Hg in bead-injected eyes. Histochemical analysis of eyes with elevated IOP revealed significant changes in the structure of the optic nerve. This included disruption of the normal honeycomb arrangement of GFAP-positive astrocytes as well as an ~42% loss of SMI32-positive axons. There was a significant reduction in the number of Brn3a-positive RGCs in mid-peripheral (~26% loss) and peripheral (~65% loss) regions. However, RGC loss in central retinal regions was only ~9%. Double labeling of retinal whole mounts for Brn3a and SMI32 to visualize alpha RGCs, revealed significant pruning of dendrites in microbead-injected eyes. Immunostaining of microbead-injected retinas for iba1 revealed microglia with rod-like appearance in the GCL and enlarged somas and retracted thick processes in the IPL/OPL, all characteristic of their activated state. Consistent with the morphological results, the amplitude of the photopic negative response (PhNR) of the ERG, used as a diagnostic index of RGC activity, was significantly reduced in glaucomatous retinas as compared to normal eyes.
Our results show that induced ocular hypertension of marmoset eyes with microbeads produces a reliable non-human primate model of glaucoma that should be useful in studies of underlying mechanisms and treatments of the disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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