Update on Nicotinamide and Its Application in the Management of Glaucoma

Glaucoma continues to be a primary contributor to permanent vision loss worldwide, frequently advancing even when intraocular pressure management is clinically adequate. Accumulating research emphasizes the metabolic susceptibility of retinal ganglion cells (RGCs), specifically concerning the progressive depletion of nicotinamide adenine dinucleotide (NAD⁺), a pivotal coenzyme fundamental to mitochondrial energy production and cellular survival mechanisms. As a key biosynthetic precursor in NAD⁺ synthesis pathways, nicotinamide (NAM), a form of vitamin B3, has exhibited significant neuroprotective properties across various preclinical experimental models and preliminary clinical investigations, demonstrating enhanced preservation of RGC morphology and physiological function. This comprehensive review systematically examines the current body of evidence supporting NAM's therapeutic utility in glaucomatous neuroprotection, focusing particularly on underlying metabolic pathways, obstacles in clinical translation, and prospective therapeutic applications. Through systematic integration of data from cellular and molecular research, animal experimental studies, and population-based epidemiological investigations, we establish a conceptual framework for repurposing NAM as an innovative complementary therapeutic strategy in comprehensive glaucoma care, addressing key considerations for future clinical development including optimal dosing strategies, delivery mechanisms, and patient selection criteria for maximizing therapeutic outcomes in this challenging neurodegenerative condition.