Transient functional preservation precedes retinal ganglion cell degeneration following optic nerve crush

Optic nerve crush (ONC) induces progressive retinal ganglion cell (RGC) degeneration; however, the temporal relationship between functional impairment and structural loss remains incompletely understood. This study investigated early changes in retinal function and subtype-specific RGC responses following ONC to determine whether retinal activity is preserved before substantial RGC degeneration.

Adult Sprague-Dawley rats underwent ONC and were examined at 1, 3, 7, and 14 days after injury. Retinal function was assessed using electroretinography (ERG), photopic negative response (PhNR), and multi-electrode array (MEA) recordings. RGC survival was quantified by Fluoro-Gold labeling, while microglial activation and oxidative stress-related markers were evaluated by immunofluorescence.

RGC survival remained largely preserved during the first 3 days following ONC but declined markedly at days 7 and 14. MEA recordings showed relative preservation of light-evoked responses at day 3, followed by progressive reductions in responsiveness and spontaneous firing at later stages. PhNR amplitudes showed a similar trend, although the changes did not reach statistical significance. Subtype analysis revealed differential vulnerability, with ONOFF-RGCs exhibiting greater reductions in proportion and functional responses, whereas ON-RGCs accounted for an increasing proportion of surviving cells over time. Microglial activation increased during the degenerative phase, while the oxidative damage marker 8-OHG immunoreactivity appeared elevated early after injury. No obvious changes were detected in NQO-1 or SOD-2 expression.

Retinal function remained relatively preserved during the first 3 days following ONC despite ongoing injury and before substantial RGC loss occurred. ONOFF-RGCs exhibited greater vulnerability than other functional subtypes. These findings identify an early post-injury period preceding substantial RGC degeneration and provide insight into the temporal dynamics of RGC dysfunction following optic nerve injury.