Abstract
Purpose :
The health and transparency of the cornea is critically dependent on the nervous system that regulates the ocular surface. Corneal sensory innervation plays an essential role in maintaining homeostasis, responding to injury and regulating hydration. This study investigates the neuroprotective potential of three compounds against oxidative damage with the aim of advancing innovative therapies for visual health.
Methods :
Corneas of Wistar rats were overexposed to blue light (470 nm, 400 lux, 18 N/m2) for 4 hours daily for 10 days to induce oxidative damage. Neuroprotective compounds, including N-acetylcysteine (NAC), rapamycin, and crocin, were administered topically to the eyes before and during this period. Rats were humanely euthanized and corneal innervation and neuronal degenerative events were analyzed. All procedures were performed according to the ARVO Statement for the Use of Animals in Research and the corresponding Spanish and EU guidelines.
Corneal wholemounts and cross sections were used to evaluate nerve fibers and ocular surface integrity. In addition, primary trigeminal ganglion neuronal cultures were treated with neuroprotectants prior to induction of oxidative damage by sodium azide, rotenone, and blue light. Immunofluorescence techniques using specific antibodies against β-tubulin III, phosphorylated tau, CaMKII, and hemoxygenase-1 (HO-1) were used to analyze neuronal degeneration and oxidative stress.
Results :
Neuroprotectants showed significant benefits in neuronal cultures, including HO-1 enzyme activation, preserved mitochondrial integrity, decreased CaMKII expression and microtubule stability. Whole mount preparations showed improved microtubule preservation and increased density of corneal subbasal fibers in rats treated with neuroprotectants.
Conclusions :
This study suggests a beneficial effect of these compounds on corneal innervation against oxidative damage. NAC, rapamycin, and crocin exhibited neuroprotective effects on neuronal nerve fibers, potentially preventing oxidative damage to the ocular surface's innervation.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.