Abstract
Abstract
Purpose : Oxidative stress, which is characterized by insufficient antioxidant defenses and disrupted neurotrophic support, is an underlying mechanism in glaucomatous retinal ganglion cells degeneration (Tezel, Prog Retin Eye Res, 25:490, 2006). The transcription factor, Nrf2 maintains redox homeostasis, and its deficiency contributes to glaucomatous damage (Zhang et al., Biomedicines 11:1512, 2023; Rohowetz et al., Int. J. Mol. Sci. 19: 3362, 2018). Simultaneously, neurotrophic imbalance—specifically elevated pro-BDNF, which signals apoptosis (Lin et al., eLife 4:e11692, 2015; Yang et al., Nat. Neurosci. 12:113, 2009) can promote degeneration, while mature BDNF supports neuronal survival (Huang et al., Annu. Rev. Biochem., 72:609, 2003; Schecterson et al., Dev. Neurobiol. 70:332, 2010). Since endogenous gasotransmitters, NO and H2S modulate oxidative and neuroprotective pathways, this study evaluated whether AMP, a novel NO/H2S-donor can protect bovine retina from H2O2-induced stress via activation of Nrf2 and reduction in pro-BDNF expression, ex vivo.
Methods : Bovine eyeballs were intravitreally injected with either AMP (10-11 to 10-6 M), H2O2 (10-3 &10-4 M), or AMP in the presence of H2O2. Retinas were processed for H&E staining or Western blot analysis. p-Nrf2 was measured in control, AMP-, H2O2-, and AMP + H2O2-treated groups. Pro-BDNF was assessed in control, H2O2 (10-3 M)-, and AMP (10-7 & 10-6 M) + H2O2-treated groups. β-actin served as loading control; bands were quantified using ImageJ.
Results : AMP preserved retinal morphology, while H2O2 (10-3 &10-4 M) induced outer segment loss and structural disruption of the retina. AMP (10-11&10-10M) significantly (p<0.0001; n=3) enhanced p-Nrf2 expression by 1380% and 1620%, respectively. Whereas H2O2 (10-3) reduced Nrf2 levels, AMP (10-11& 0-10M) significantly (p<0.001; n=3) upregulated its expression from 0.390 (H2O2) to 1.84 (371.8%) and 1.98 (407.7%), respectively. Moreover, AMP (10-7 & 10-6 M) significantly (p<0.001;n=3) reversed H2O2-mediated change in pro-BDNF, suggesting preservation of mature BDNF-mediated neurotrophic support.
Conclusions : AMP protected bovine retina from oxidant stress via an upregulation of the transcription factor, Nrf2 and downregulation of the pro-apoptotic factor, pro-BDNF. AMP is a potential multifunctional drug candidate that targets both oxidative and neurotrophic pathways.
This abstract was presented at the 2026 ARVO Annual Meeting, held in Denver, CO, May 3-7, 2026.