# Rotenone-Induced Optic Nerve Damage and Retinal Ganglion Cell Loss in Rats

## TL;DR

This study shows how rotenone, a mitochondrial inhibitor, causes optic nerve damage and retinal cell loss in rats, providing insights into optic neuropathy.

## Contribution

The study reveals that rotenone-induced optic nerve damage involves axonal degeneration and RGC loss, linked to oxidative stress and calcium signaling.

## Key findings

- Rotenone caused axonal swelling, degeneration, and reactive gliosis in optic nerves.
- Retinal ganglion cell axons showed thinning, fragmentation, and reduced soma numbers.
- Mitochondrial dysfunction via rotenone contributes to optic neuropathy pathogenesis.

## Abstract

Rotenone is a mitochondrial complex I inhibitor that causes retinal degeneration. A study of a rat model of rotenone-induced retinal degeneration suggested that this model is caused by indirect postsynaptic N-methyl-D-aspartate (NMDA) stimulation triggered by oxidative stress-mediated presynaptic intracellular calcium signaling. To elucidate the mechanisms by which rotenone causes axonal degeneration, we investigated morphological changes in optic nerves and the change in retinal ganglion cell (RGC) number in rats. Optic nerves and retinas were collected 3 and 7 days after the intravitreal injection of rotenone. The cross-sections of the optic nerves were subjected to a morphological analysis with axon quantification. The axons and somas of RGCs were analyzed immunohistochemically in retinal flatmounts. In the optic nerve, rotenone induced axonal swelling and degeneration with the incidence of reactive gliosis. Rotenone also significantly reduced axon numbers in the optic nerve. Furthermore, rotenone caused axonal thinning, fragmentation, and beading in RGCs on flatmounts and decreased the number of RGC soma. In conclusion, the intravitreal injection of rotenone in rats induced morphological abnormities with a reduced number of optic nerve axons and RGC axons when the RGC somas were degenerated. These findings help elucidate the pathogenesis of optic neuropathy induced by mitochondrial dysfunction.