Differential Susceptibility of Rat Retinal Ganglion Cells Following Optic Nerve Crush

Abstract

Retinal ganglion cells (RGCs) are a heterogeneous group of cells, comprised of numerous subpopulations, that work together to send visual information to the brain. In numerous blinding disorders termed optic neuropathies, RGCs are the main cell type affected leading to degeneration of these cells and eventual loss of vision. Previous studies have identified and characterized RGC subtypes in numerous animal systems, with only a handful of studies demonstrating their differential loss in response to disease and injury. Thus, efforts of the current study utilized an optic nerve crush (ONC) model to characterize the loss of RGCs and disease phenotypes associated with this injury. Additionally, the loss of RGC subtypes including direction selective-, alpha-, and ip-RGCs following ONC was explored. Results of this study demonstrated the differential loss of RGC subtypes with a high susceptibility for loss of alpha-and direction selective-RGCs and the preferential survival of ip-RGCs following ONC and allows for the establishment of additional studies focused on mechanisms and loss of these cells in optic neuropathies. Additionally, these results put important emphasis on the development of therapeutics targeted at the loss of specific subtypes as well as cellular replacement following injury and disease.

Indirect traumatic optic neuropathy after head trauma in adolescent male mice is associated with behavioral visual impairment, neurodegeneration, and elevated endoplasmic reticulum stress markers at acute and subacute times

“…One possibility may be differences in susceptibility of RGC subtypes to this injury, as this has been shown in other optic nerve models. [60,61] Moreover, there is increased astrogliosis in both vLGN and dLGN both seven and thirty DPI. This may suggest that astroglia are playing a larger role in the detrimental effects of the injury subacutely than the neuroinflammation implied by morphologically activated microglia.…”

Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice

“…While we are uncertain as to why the two regions differ at different time points, it does seem that projections to the dorsal LGN and ventral LGN respond to this injury differently. One possibility may be differences in the susceptibility of retinal cell subtypes to injury, as this has been shown in other optic nerve models [ 66 , 67 ]. Moreover, astrogliosis is more consistent across both lateral geniculate nuclei divisions, which may suggest that astroglia are playing a larger role in the detrimental effects of the injury sub acutely.…”

Distribution of prototypical primary cilia markers in subtypes of retinal ganglion cells

“…Additionally, stabilization of cilia structure and stimulation of the Shh pathway each had a protective effect on RGCs after injury (Choi et al., 2019; Wu et al., 2010). Interestingly, more than 30–60 subtypes of RGCs have been described based on their morphology, response to light, and molecular signature (Rheaume et al., 2018; Sanes & Masland, 2015), and some RGC subtypes were identified as more susceptible to cell death in response to increased IOP (Daniel et al., 2018; Della Santina & Ou, 2017; Ou et al., 2016; VanderWall et al., 2018). How cilia dysfunction of RGCs contributes to retinal degeneration is unclear, and more fundamental questions about RGC cilia remain.…”