Loss of optic nerve oligodendrocytes during maturation alters retinal organization

Authors

Annika Balraj, Department of Anatomy and Cell Biology, The George Washington University, School of Medicine and Health Sciences, Washington, D.C., USA.
Cheryl Clarkson-Paredes, Department of Anatomy and Cell Biology, The George Washington University, School of Medicine and Health Sciences, Washington, D.C., USA.
Robert H. Miller, Department of Anatomy and Cell Biology, The George Washington University, School of Medicine and Health Sciences, Washington, D.C., USA. Electronic address: rhm3@gwu.edu.

Document Type

Journal Article

Publication Date

6-24-2023

Journal

Experimental eye research

Volume

233

DOI

10.1016/j.exer.2023.109540

Keywords

Displaced amacrine cell; Myelination; Nerve conduction; Oligodendrocyte loss; Retinal ganglion cell

Abstract

The myelin sheath facilitates signal conduction along axons in white matter tracts, and when disrupted, can result in significant functional deficits. Demyelination, observed in diseases like multiple sclerosis and optic neuritis, are associated with neural degeneration, however the extent of this damage on upstream circuitry is not well understood. Here we use the MBP-iCP9 mouse model to induce selective oligodendrocyte ablation in the optic nerve at P14 via a chemical inducer of dimerization (CID), resulting in partial demyelination of retinal ganglion cell (RGC) axons with minimal inflammation after two weeks. Oligodendrocyte loss reduced axon diameter and altered compound action potential waveforms, blocking conduction in the slowest-conducting axon populations. Demyelination resulted in disruptions to the normal composition of the retina, including reduced density of RBPMS+, Brn3a+, and OFF-transient RGCs, thinning of the IPL, and reduced density of displaced amacrine cells. The INL and ONL were unaffected by oligodendrocyte loss, suggesting that demyelination-induced deficits in this model are specific to the IPL and GCL. These results show that a partial demyelination of a subpopulation of RGC axons disrupts optic nerve function and affects the organization of the retinal network. This study highlights the significance of myelination in maintaining upstream neural connectivity and provides support for targeting neuronal degeneration in treatments of demyelinating diseases.

APA Citation

Balraj, Annika; Clarkson-Paredes, Cheryl; and Miller, Robert H., "Loss of optic nerve oligodendrocytes during maturation alters retinal organization" (2023). GW Authored Works. Paper 2688.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2688

Department

Anatomy and Regenerative Biology