The Susceptibility of Retinal Ganglion Cells to Optic Nerve Injury is Type Specific

Ning Yang,Ning Tian,Brent K Young,Ping Wang

doi:10.3390/cells9030677

Ning Yang, Ning Tian + Show 2 more

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https://doi.org/10.3390/cells9030677

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Journal: Cells	Publication Date: Mar 10, 2020
Citations: 24	License type: CC BY 4.0

Affiliation: University of Utah, VA Salt Lake City Healthcare System

Abstract

Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several genetically identified RGC types to N-methyl-D-aspartate (NMDA) excitotoxicity differs significantly. In this study, we characterize the susceptibility of the same RGC types to optic nerve crush (ONC). We show that the susceptibility of these RGC types to ONC varies significantly, in which BD-RGCs are the most resistant RGC type while W3-RGCs are the most sensitive cells to ONC. We also show that the survival rates of BD-RGCs and J-RGCs after ONC are significantly higher than their survival rates after NMDA excitotoxicity. These results are consistent with the conclusion that the susceptibility of RGCs to ONC varies in an RGC type-dependent manner. Further, the susceptibilities of the same types of RGCs to ONC and NMDA excitotoxicity are significantly different. These are valuable insights for understanding of the selective susceptibility of RGCs to various pathological insults and the development of a strategy to protect RGCs from death in disease conditions.

Highlights

In mammals, retinal ganglion cells (RGCs) are the only output neurons that conduct visual signals from the eyes to the brain
BD-RGCs and αRGCs are significantly lower than the susceptibility of the entire RGC population; the susceptibility of JamB-expressing RGCs (J-RGCs) is not different from the susceptibility of the whole RGC population
We show that the survival rates of BD-RGCs, J-RGCs and W3-RGCs after optic nerve crush (ONC) are significantly higher than their survival rates after NMDA excitotoxicity

Summary

Introduction

Retinal ganglion cells (RGCs) are the only output neurons that conduct visual signals from the eyes to the brain. RGC death occurs in many blinding retinal diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that RGCs are susceptible to various injuries in an RGC type-dependent manner. In experimental models of ocular hypertension, OFF RGCs exhibit higher rates of cell death than ON RGCs [10,11,12], and mono-laminated ON RGCs are found to be more susceptible to elevated intraocular pressure (IOP). In models of optic nerve injury, OFF RGCs are more susceptible than ON RGCs, and ON-sustained RGCs seem to be more vulnerable than ON-transient

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