Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy; Headache Center and Clinical Pharmacology Unit, Careggi University Hospital, Florence, Italy.
Trends Pharmacol Sci. 2023 Dec;44(12):869-879. doi: 10.1016/j.tips.2023.09.010. Epub 2023 Oct 23.
Clinical evidence shows that intraocular hypertension is not the primary pathogenetic event of glaucoma, whereas early neurodegeneration of retinal ganglion cells (RGCs) represents a key therapeutic target. Unfortunately, failure of clinical trials with neuroprotective agents, in particular those testing the anti-excitotoxic drug memantine, generated widespread skepticism regarding the possibility of counteracting neurodegeneration during glaucoma. New avenues for neuroprotective approaches to counteract glaucoma evolution have been opened by the identification of a programmed axonal degeneration (PAD) program triggered by increased nicotinamide mononucleotide (NMN)/NAD concentration ratio. Positive results of proof-of-concept clinical studies based on sustaining axonal NAD homeostasis facilitated the design of Phase 2/3 trials. Here, I share my opinion on how neurodegeneration in glaucoma should be put into context, together with an appraisal of the pharmacological rationale of NAD-supporting therapies for use during glaucoma progression.
临床证据表明，眼内高压并不是青光眼的主要发病事件，而视网膜神经节细胞（RGCs）的早期神经退行性变则代表了一个关键的治疗靶点。不幸的是，神经保护剂临床试验的失败，特别是那些测试抗兴奋毒性药物美金刚的临床试验，使得人们对在青光眼期间对抗神经退行性变的可能性产生了广泛的怀疑。通过鉴定由烟酰胺单核苷酸（NMN）/NAD 浓度比升高引发的程序性轴突变性（PAD）程序，为对抗青光眼进展的神经保护方法开辟了新的途径。在这里，我分享了我对如何将青光眼的神经退行性变置于适当背景下的看法，并评价了在青光眼进展期间使用 NAD 支持疗法的药理学原理。
