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bioRxiv · 10.1101/2024.01.18.576306

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

Hong, E.·Tian, F.·Glynn, C.·Tsekov, S.·Huang, S.·Zhou, S.·He, Z.·Rao, S.·Wang, Q.
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Abstract

Fluid transport through the trabecular meshwork is a major regulator of intraocular pressure in healthy and glaucomatous eyes. Existing microbead occlusion models enable in vivo study of pressure-related glaucomatous pathology, but their long-term reliability is limited by inadequate bead-tissue interface design. Inspired by the graded porous architecture and fluid-transport function of the trabecular meshwork, we develop an injectable Viscobeads platform for sustained modulation of aqueous humor outflow. These composite microbeads integrate a non-degradable polystyrene core for structural support with a biodegradable poly(lactic-co-glycolic acid) viscoelastic shell that improves mechanical adaptation to heterogeneous trabecular meshwork fenestrations. This biologically informed design enhances outflow obstruction and enables stable IOP elevation for at least 8 weeks after a single injection. In mice, Viscobeads induce sustained ocular hypertension (average 21.4 mm Hg) and lead to a 34% loss of retinal ganglion cells by day 56. Pattern electroretinogram and flash visual evoked potential measurements further reveal early retinal ganglion cell dysfunction followed by later visual pathway impairment. Beyond disease induction, this platform supports in vivo gene screening for retinal ganglion cell survival and identifies altered sleep behavior during glaucoma progression. This work establishes a materials-driven strategy for chronic ocular hypertension modeling and therapeutic evaluation.

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Hong, E., Tian, F., Glynn, C., Tsekov, S., Huang, S., Zhou, S., He, Z., Rao, S., Wang, Q.. 2024-01-23. Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model. https://doi.org/10.1101/2024.01.18.576306

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