Modelling and treating dysregulated fibrosis in primary open angle glaucoma

Hill, Lisa Jayne (2015). Modelling and treating dysregulated fibrosis in primary open angle glaucoma. University of Birmingham. Ph.D.

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Abstract

Introduction
A risk factor for POAG is elevated intraocular pressure induced by reduced outflow of aqueous humour through the fibrosed trabecular meshwork, causing retinal ganglion cell death. This study aimed to: 1) create a rodent model of increased intraocular pressure by inducing trabecular meshwork fibrosis; 2) evaluate the ability of the anti-fibrotic agent, Decorin to diminish trabecular meshwork fibrosis and lower intraocular pressure; 3) correlate these findings to RCG survival and 4) investigate alternative translational methods for delivery of Decorin into the eye.

Methods
Fibrotic agents, kaolin or TGF-β, were intracamerally injected to induce fibrosis and intraocular pressure elevation. Following this human recombinant Decorin was administered intracamerally. Fibrosis was measured by immunohistochemistry and electron microscopy. Retinal ganglion cell counts were performed from retinal whole mounts.

Results
TGF-β induced fibrosis of the trabecular meshwork leading IOP elevation and retinal ganglion cell death, thus providing a reliable in vivo model of the ocular fibrosis. Decorin reversed the TGF-β induced fibrosis in the trabecular meshwork, lowered intraocular pressure and indirectly prevented retinal ganglion cell death. Decorin was successfully delivered to the anterior chamber in an eye drop formulation.

Conclusion
Decorin may be an effective treatment to preserving visual function in patients with POAG.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):