From Nature to Treatment: The Impact of Pterostilbene on Mitigating Retinal Ischemia–Reperfusion Damage by Reducing Oxidative Stress, Inflammation, and Apoptosis

Abstract

Retinal ischemia–reperfusion (I/R) injury is a critical pathogenic mechanism in various eye diseases, and an effective therapeutic strategy remains unresolved. Natural derivatives have recently reemerged; therefore, in our present study, we examined the potential therapeutic effects of a stilbenoid that is chemically related to resveratrol. Pterostilbene, recognized for its anti-inflammatory, anti-carcinogenic, anti-diabetic, and neuroprotective properties, counteracts oxidative stress during I/R injury through various mechanisms. This study explored pterostilbene as a retinoprotective agent. Male Sprague Dawley rats underwent retinal I/R injury and one-week reperfusion and were treated with either vehicle or pterostilbene. After this functional electroretinographical (ERG) measurement, Western blot and histological analyses were performed. Pterostilbene treatment significantly improved retinal function, as evidenced by increased b-wave amplitude on ERG. Histological studies showed reduced retinal thinning and preserved the retinal structure in the pterostilbene-treated groups. Moreover, Western blot analysis revealed a decreased expression of glial fibrillary acidic protein (GFAP) and heat shock protein 70 (HSP70), indicating reduced glial activation and cellular stress. Additionally, the expression of pro-apoptotic and inflammatory markers, poly(ADP-ribose) polymerase 1 (PARP1) and nuclear factor kappa B (NFκB) was significantly reduced in the pterostilbene-treated group. These findings suggest that pterostilbene offers protective effects on the retina by diminishing oxidative stress, inflammation, and apoptosis, thus preserving retinal function and structure following I/R injury. This study underscores pterostilbene’s potential as a neuroprotective therapeutic agent for treating retinal ischemic injury and related disorders.