Abstract
Glaucoma is a neurodegenerative disease with retinal ganglion cell (RGC) loss, optic nerve degeneration and subsequent vision loss. There are about 30 different subtypes of RGCs whose response to glaucomatous injury is not well characterized. The purpose of this study was to evaluate the response of 4 RGC subtypes in a mouse model of optic nerve crush (ONC). In this study, we also evaluated the pattern of axonal degeneration in RGC subtypes after nerve injury. We found that out of the 4 subtypes, transient-Off α RGCs are the most susceptible to injury followed by On–Off direction selective RGCs (DSGC). Non-image forming RGCs are more resilient with ipRGCs exhibiting the most resistance of them all. In contrast, axons degenerate irrespective of their retinal soma after ONC injury. In conclusion, we show that RGCs have subtype specific cell death response to ONC injury and that RGC axons disintegrate in an autonomous fashion undergoing Wallerian degeneration. These discoveries can further direct us towards effective diagnostic and therapeutic approaches to treat optic neuropathies, such as glaucoma.
Highlights
Glaucoma is a group of optic neuropathies with clinical manifestations including cupping of the optic disc, thinning and loss of the retinal nerve fiber layer, and characteristic visual field defects[1]
Axonal degeneration and retinal ganglion cells (RGC) death occurs leading to loss of vision and irreversible blindness[1,6]
We show that the 4 RGC subtypes we evaluated have different cell death sensitivities to optic nerve crush (ONC) injury
Summary
Glaucoma is a group of optic neuropathies with clinical manifestations including cupping of the optic disc, thinning and loss of the retinal nerve fiber layer, and characteristic visual field defects[1]. It is the leading cause of irreversible blindness worldwide[2]. The many similarities between a human and mouse eye, and the availability of various genetic tools, have made it possible to study glaucoma and its phenotypes in mice[13, 14] One such tool is the development of transgenic mice expressing GFP in individual subtypes of RGCs15–17. By subjecting these animals to glaucomatous insults, we can study the effect of this injury exclusively in each particular subtype and have a deeper understanding of susceptibility of these RGCs to glaucomatous insults
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