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

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.

A Dietary Combination of Forskolin with Homotaurine, Spearmint and B Vitamins Protects Injured Retinal Ganglion Cells in a Rodent Model of Hypertensive Glaucoma

“…No regional differences in RGC loss have been observed in either the retina or the RGC axons of DBA/2J mice [45], while major RGC loss in the peripheral retina has been detected after microbead injection into the mouse anterior chamber [35]. In this line, the susceptibility of RGCs to ONC has been found to depend on RGC types [46].…”

RGC and Vision Loss From Traumatic Optic Neuropathy Induced by Repetitive Closed Head Trauma Is Dependent on Timing and Force of Impact

“…Studies show that susceptibility of RGCs to various pathological insults or injuries are subtype specific. 29 Therefore, it is possible that selective subsets of RGCs in the retina that are responsible for optokinetic responses such as direction-selective ganglion cells, may adapt or may become active after an injury shock period. Alternatively, surviving RGCs may increase in visual responses by sprouting new synaptic connections.…”

Probing ON and OFF Retinal Pathways in Glaucoma Using Electroretinography

“…One possible way to reconcile these discrepancies in differential RGC susceptibility may require taking into account that these occur after different types and magnitudes of injury, such as varying degrees and duration of IOP elevation or optic nerve injury, differences in rodent strains, and analysis techniques as highlighted in the Table. For instance, one group used the same mouse line but found differences in RGC type susceptibilities using different experimental modelsone model used a glutamate agonist injection and the other used an optic nerve crush model. 46,47 Differences observed across models may reconcile within a larger framework, for example, if there is only a short temporal window to counteract the injuring stimulus before reversible RGC damage triggers degeneration. An additional limitation of examining IOP changes as the main driver of injury is that these experiments only measure snapshots of the IOP.…”

“…For instance, one group used the same mouse line but found differences in RGC type susceptibilities using different experimental models—one model used a glutamate agonist injection and the other used an optic nerve crush model. 46 , 47 Differences observed across models may reconcile within a larger framework, for example, if there is only a short temporal window to counteract the injuring stimulus before reversible RGC damage triggers degeneration. An additional limitation of examining IOP changes as the main driver of injury is that these experiments only measure snapshots of the IOP.…”