The number of Myo/Nog cells increases in a murine model of glaucoma

Abstract

Purpose : Myo/Nog cells, named for their expression of the skeletal muscle specific transcription factor MyoD and bone morphogenetic protein inhibitor noggin, are critical regulators of embryonic development, including eye morphogenesis. In the normal adult eye, Myo/Nog cells are present in low numbers throughout the anterior segment and retina. A neuroprotective function for Myo/Nog cells was demonstrated in the retina compromised by hypoxia and excessive light. The goal of this project was to examine the behavior of Myo/Nog cells in response to increased intraocular pressure and retinal damage in a mouse model of glaucoma.

Methods : Induction of glaucoma was performed in the wildtype C57BL/6J strain of mice by injecting 2 μL of microbeads into the anterior chamber of the right eye. With an external magnet, the microbeads were drawn to the peripheral edge of the iris to block drainage of aqueous humor from the Canal of Schlemm. The left eye of each mouse was injected with 2 μL of PBS to serve as a control. Ocular Computer Topography (OCT) and electroretinography (ERG) were performed one week prior to injection to obtain baseline measurements of retinal layer thickness and function. Intraocular pressure (IOP) was measured before and every 3 days, after injection of microbeads, using a Tonopen. Eyes were harvested 25 days post injection. Cryosections were labeled with the G8 antibody that specifically binds to Myo/Nog cells. The numbers and locations of Myo/Nog cells in treated and control eyes were counted in cryosections along the length of the retina.

Results : Injection of microbeads, but not PBS, resulted in increased intraocular pressure, beginning 3 days after injection. OCT imaging revealed that the ganglion cell and nerve fiber layers (GCL-NFL) decreased coincident with increased IOP. The number of Myo/Nog cells was significantly greater in in the choroid, and in the outer plexiform and inner nuclear layer of the retina in glaucomatous eyes compared to control eyes.

Conclusions : Injection of microbeads into the anterior chamber and the resulting increase in IOP induce morphological and functional changes in the mouse retina that resemble features of disease progression in glaucoma. As in other forms of retinopathy, Myo/Nog cells respond to stress and increase in areas of injury. This model is useful for studying a potential neuroprotective role for Myo/Nog cells in glaucoma.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.