Surface moieties drive the superior protection of curcumin-derived carbon quantum dots against retinal ischemia-reperfusion injury.

Despite the recognized neuroprotective benefits of curcumin, its clinical utility is constrained by poor bioavailability and high cytotoxicity at effective doses. This study evaluates the therapeutic potential of curcumin-derived carbon quantum dots (Cur-CQDs) for retinal protection against ischemia-reperfusion (IR) injury in rats. Cur-CQDs were synthesized via mild pyrolysis at varying temperatures and assessed for efficacy in rat retinal ganglion cells and a model of retinal IR injury. The Cur-CQDs, particularly those synthesized at 150 °C, displayed significant reductions in apoptosis in retinal tissues, as indicated by TUNEL assays, immunofluorescence localization of HIF-α, CD68, BCL-2, and Grp78, and Western blot analysis for HO-1, Grp78, CHOP, caspase 3, and Nrf2. These results suggest that Cur-CQDs not only enhance cell survival and reduce inflammation but also decrease oxidative and endoplasmic reticulum stress markers. Mechanistic insights reveal that Cur-CQDs modulate pathways involved in oxidative stress, apoptosis, and inflammation, specifically through the upregulation of BCL-2 and HO-1 and the downregulation of CHOP, caspase-3, and endoplasmic reticulum stress markers. The identification of cinnamic acid-, anisole-, guaiacol, and ferulic acid-like structures on Cur-CQDs' surfaces may contribute to their superior antioxidative and anti-inflammatory activities. Collectively, these findings position Cur-CQDs as a promising approach for treating retinal IR injuries, enhancing curcumin's bioavailability and therapeutic efficacy, and paving new pathways in ocular neuroprotection research and potential clinical applications.