Abstract
Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP) resulting in progressive loss of retinal ganglion cells (RGCs) and optic nerve degeneration, leading to blindness. New therapeutic approaches that better preserve the visual field by promoting survival and health of RGCs are highly needed since RGC death occurs despite good IOP control in glaucoma patients. We have developed a novel approach to reliably induce chronic IOP elevation in mouse using a photopolymerizable biomatrix, hyaluronic acid glycidyl methacrylate. This is achieved by rapid in vivo crosslinking of the biomatrix at the iridocorneal angle by a flash of ultraviolet A (UVA) light to impede the aqueous outflow pathway with a controllable manner. Sustained IOP elevation was induced after a single manipulation and was maintained at ~45% above baseline for >4 weeks. Significant thinning of the inner retina and ~35% reduction in RGCs and axons was noted within one month of IOP elevation. Optic nerve degeneration showed positive correlation with cumulative IOP elevation. Activation of astrocytes and microglia appeared to be an early event in response to IOP elevation preceding detectable RGC and axon loss. Attenuated glial reactivity was noted at later stage where significant RGC/axon loss had occurred suggesting astrocytes and microglia may play different roles over the course of glaucomatous degeneration. This novel murine glaucoma model is reproducible and displays cellular changes that recapitulate several pathophysiological features of glaucoma.
Highlights
Glaucoma is the leading cause of irreversible blindness loss worldwide, it has been estimated that one in 40 adults over the age of 40 suffers from glaucoma [1]
Polymerization of hyaluronic acid glycidyl methacrylate (HAMA) at the iridocorneal angle induced sustained intraocular pressure (IOP) elevation Animals were randomly divided into four groups: (1) the ocular hypertension (OHT) group received microinjection of 2% (w/v) HAMA mixed with microbeads into the anterior chamber followed by in vivo ultraviolet A (UVA) crosslink; (2) one control group received phosphate buffered saline (PBS) followed by UVA exposure; (3) another control group received injection of 2% HAMA without microbeads or UVA crosslink; and (4) a naive group with no treatment
The HAMA was immediately polymerized into a transparent gel form by exposing the cornea to a defined UVA light (365nm wavelength) at a distance of 10cm for 10 s, the microbeads were immobilized into the HAMA gel to enable long term visualization in the anterior chamber
Summary
Glaucoma is the leading cause of irreversible blindness loss worldwide, it has been estimated that one in 40 adults over the age of 40 suffers from glaucoma [1]. Glaucoma is a multifactorial central nervous system (CNS) neurodegenerative disease characterized by cupping of the optic disc, progressive loss of retinal ganglion cells (RGCs) and their axons in the optic nerve tract. Elevated IOP is one major risk factor for primary open angle glaucoma (POAG)–the most common form of glaucoma accounting for 74% of all types[2]; glaucoma can develop. Glaucoma model induced by photopolymerizable biomatrix collection and analysis, or preparation of the manuscript. The specific roles of these authors are articulated in the ’author contributions’ section
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
