Characterization of Non-alpha Retinal Ganglion Cell Injury Responses Reveals a Possible Block to Restoring IpRGC Function

Overview

Journal Exp Neurol

Specialty Neurology

Date 2022 Jul 23

PMID 35870522

Authors

John L Hunyara

Sierra Foshe

Supraja G Varadarajan

Katherine D Gribble

Andrew D Huberman

Alex L Kolodkin

Affiliations

Soon will be listed here.

Abstract

Visual impairment caused by retinal ganglion cell (RGC) axon damage or degeneration affects millions of individuals throughout the world. While some progress has been made in promoting long-distance RGC axon regrowth following injury, it remains unclear whether RGC axons can properly reconnect with their central targets to restore visual function. Additionally, the regenerative capacity of many RGC subtypes remains unknown in part due to a lack of available genetic tools. Here, we use a new mouse line, Sema6A, that labels On direction-selective RGCs (oDSGCs) and characterize the survival and regenerative potential of these cells following optic nerve crush (ONC). In parallel, we use a previously characterized mouse line, Opn4, to answer these same questions for M1 intrinsically photosensitive RGCs (ipRGCs). We find that both M1 ipRGCs and oDSGCs are resilient to injury but do not display long-distance axon regrowth following Lin28a overexpression. Unexpectedly, we found that M1 ipRGC, but not oDSGC, intraretinal axons exhibit ectopic branching and are misaligned near the optic disc between one- and three-weeks following injury. Additionally, we observe that numerous ectopic presynaptic specializations associate with misguided ipRGC intraretinal axons. Taken together, these results reveal insights into the injury response of M1 ipRGCs and oDSGCs, providing a foundation for future efforts seeking to restore visual system function following injury.

Citing Articles

Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the mouse inner retina.

James R, Hamilton N, Huffman L, Brown M, Neckles V, Pasterkamp R Development. 2024; 151(22).

PMID: 39495936 PMC: 11634039. DOI: 10.1242/dev.204293.

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