Mol Neurobiol. 2025 Jul 22. doi: 10.1007/s12035-025-05243-3. Online ahead of print.
ABSTRACT
Glaucoma is a globally recognized leading cause of irreversible blindness, and its progression is closely associated with retinal ganglion cell (RGC) degeneration and mitochondrial dysfunction. Recently, there has been growing interest in the role of nicotinamide adenine dinucleotide (NAD +) and its regulatory enzyme CD38 in the pathogenesis and progression of glaucoma. NAD + plays a critical role in cellular energy metabolism and signal transduction, and its depletion is strongly linked to mitochondrial dysfunction and neurodegenerative diseases. The function of CD38 in glaucoma primarily involves modulating oxidative stress, inflammatory responses, and apoptosis by regulating NAD + levels. With advancing age, the expression of CD38 tends to increase, leading to reduced NAD + levels. Studies have demonstrated that inhibition or absence of CD38 can elevate NAD + levels, thereby enhancing the activity of NAD + -dependent enzymes (such as Sirt1) to protect RGCs from injury and mitigate retinal ischemia-reperfusion injury and inflammation. Furthermore, animal studies have indicated that supplementation with NAD + precursors (such as nicotinamide) can delay glaucoma progression by restoring the neuroprotective effects mediated by NAD + . This review systematically examines the interplay between NAD + and CD38 in glaucoma pathogenesis and explores potential therapeutic strategies targeting the CD38/NAD + axis. Despite promising experimental findings supporting this approach, current research still faces challenges such as drug selectivity, side effects, and validation of treatment efficacy. Future investigations into optic neuroprotection in glaucoma should focus on elucidating the precise mechanisms of the CD38/NAD + axis within retinal tissue to develop more effective glaucoma therapies.
PMID:40696206 | DOI:10.1007/s12035-025-05243-3