Stiffening the posterior rat sclera to provide neuroprotection in glaucoma

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Hannon, Bailey Grace
Ethier, C. Ross
Pardue, Machelle T.
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Glaucoma is the leading cause of irreversible blindness in the world, affecting approximately 80 million people in the year 2020. This degenerative optic neuropathy is characterized by retinal ganglion cell (RGC) death, optic nerve damage, and progressive vision loss. While the exact etiology remains elusive, elevated intraocular pressure (IOP) is a known risk factor and lowering IOP remains the only effective treatment. Elevated IOP causes deformation and remodeling of the optic nerve head (ONH) tissues, which in turn is thought to promote localized neurodegeneration. Computational and ex vivo studies have shown that scleral stiffness strongly influences deformation of the ONH, and that increasing the stiffness of the sclera surrounding the ONH (the peripapillary sclera) can significantly reduce these excessive strains. We hypothesize that by crosslinking the collagenous peripapillary sclera, we will reduce mechanical deformation in the ONH, which will in turn mitigate glaucomatous vision loss. To investigate this hypothesis, we developed a safe and efficacious scleral stiffening treatment using the collagen crosslinking agent genipin, assayed through ex vivo and in vivo experiments in healthy rat eyes. We then evaluated our treatment’s efficacy to prevent glaucomatous damage in a microbead rat model of ocular hypertension. Our results indicate that scleral stiffening protected against retinal thinning but did not show protective effects on visual or retinal function, nor preservation of RGC axons. Overall, these results demonstrate the feasibility of using genipin for a scleral stiffening treatment. The absence of a strong protective effect of genipin-induced scleral stiffening on RGC function and structure may be due to limitations in the glaucomatous rat model, in that our model does not mirror the slow progression, nor the moderate IOP elevation characteristic of clinical glaucoma.
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