# Systemic Inflammation Aggravates Retinal Ganglion Cell Vulnerability to Optic Nerve Trauma in Adult Rats

## TL;DR

Systemic inflammation worsens retinal ganglion cell loss after optic nerve injury in rats by altering microglial responses.

## Contribution

Demonstrates systemic inflammation primes retinal ganglion cells for greater injury after optic nerve trauma.

## Key findings

- Systemic LPS induces microglial activation without causing retinal ganglion cell loss in intact retinas.
- Systemic inflammation exacerbates retinal ganglion cell loss during the late acute phase after optic nerve injury.
- Inflammation increases microglial density and redistributes them toward vulnerable retinal regions after trauma.

## Abstract

Systemic inflammation is increasingly recognized as a modifier of neurodegenerative outcomes in the central nervous system; however, its impact on retinal ganglion cell (RGC) survival and retinal microglial responses following optic nerve (ON) injury in vivo remains incompletely understood. In this study, we investigated how systemic lipopolysaccharide (LPS)-induced inflammation influences retinal microglial activation and RGC vulnerability under physiological conditions and after traumatic ON damage. In adult female rats, systemic LPS administration by intraperitoneal injection induced rapid and robust microglial activation, characterized by process retraction and soma hypertrophy within hours and promoting microglial proliferation at later stages but without causing RGC loss in intact retinas. Following ON crush, systemic inflammation did not affect early RGC degeneration but significantly exacerbated neuronal loss during the late acute phase. This increased vulnerability was accompanied by a marked rise in microglial density and a pronounced redistribution of microglia toward the central retina and the ON head, a region of heightened anatomical and metabolic susceptibility. Together, these findings demonstrate that, in rats, systemic inflammation alone is insufficient to induce RGC degeneration but acts as a potent priming factor that amplifies neurodegeneration in the context of axonal injury. The temporal and spatial specificity of microglial responses underscores their context-dependent role in retinal pathology and identifies systemic inflammatory status as a critical determinant of retinal outcome after trauma. Targeted, time-dependent modulation of microglial activation may therefore represent a promising therapeutic strategy for optic neuropathies.