Myo/Nog Cells Increase in Response to Elevated Intraocular Pressure and Mitigate Ganglion Cell Death in a Mouse Model of Glaucoma

• Published in: Applied sciences 2023-11, Vol.13 (22), p.12423
• Main Authors: Lecker, Paul, Johal, Karanveer, McGrath, Alexa, Spikes, John, Bernstein, Jake, MacPherson, Victoria, Brahmbhatt, Rushil, Fadl, Nada, Weyback-Liogier, Edgar, Adams, Sarah, Souza, Rachel, Tsai, E-Jine, Martin, Mark, Gerhart, Jacquelyn, Gorski, Grezgorz, De Cecco, Federica, Heist, Brian, Egberts, Sebastian, George-Weinstein, Mindy, Bravo-Nuevo, Arturo
• Format: Article
• Language: English
• Subjects: Antibodies; Biochemistry; Blindness; Brain research; Cataract; Cell death; Ethylenediaminetetraacetic acid; Ganglion; Glaucoma; intraocular pressure; Ketamine; Mediation; Microscopy; Myo/Nog cells; Optic nerve; Pathophysiology; Phosphates; Photoreceptors; Retina; retinal ganglion cells; Surgery
• ISSN: 2076-3417; 2076-3417
• DOI: 10.3390/app132212423

Glaucoma is one of the leading causes of blindness worldwide. Decreased aqueous humor drainage causes an increase in intraocular pressure (IOP), which in turn damages the ganglion cells of the retina and optic nerve. A mouse model of glaucoma was used to examine the behavior of Myo/Nog (M/N) cells, which were previously shown to respond to cataract surgery and retinopathy induced by hypoxia, light damage, and intravitreal injection of human retinal pigment epithelial cells. M/N cells express the skeletal-muscle-specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and brain-specific angiogenesis inhibitor 1 (BAI1). Glaucoma was induced by injecting microbeads into the anterior chamber (AC) of the right eye to obstruct the flow of aqueous humor into the trabecular meshwork. IOP was elevated within three days of addition of microbeads. Loss of retinal ganglion cells (RGCs) and thinning of the ganglion cell layer–nerve fiber layer (GCL-NFL) was observed in tissue sections by day 32. The injection of microbeads resulted in an increase in BAI1-positive (+) M/N cells in the trabecular meshwork, ciliary body, canal of Schlemm, cornea, and ganglion cell layer (GCL). M/N cells ingested microbeads. The effect of further increasing the population of M/N cells on IOP and RGC loss was determined by injecting BAI1+ cells isolated from the brain into the AC of both eyes. Exogenous M/N cells prelabeled with CellTracker™ Red were found in the same tissues as the endogenous population of M/N cells in eyes with and without elevated IOP. The addition of M/N cells did not significantly reduce IOP in bead-injected eyes. However, there were significantly more RGCs and the NFL was thicker in glaucomatous eyes with M/N cell supplementation than eyes injected with phosphate-buffered saline. The numbers of RGCs and NFL thickness were similar in glaucomatous and non-glaucomatous eyes after adding M/N cells. These results demonstrate that endogenous M/N cells respond to elevated IOP in the anterior and posterior segments in response to induction of glaucoma. M/N cells’ mitigation of RGC loss may reflect a neuroprotective effect within the retina, as opposed to a significant drop in IOP.