Glaucoma: neuroprotection with NAD-based therapeutic interventions

Area of Science:

• Ophthalmology
• Neuroscience
• Pharmacology

Background:

• Glaucoma's primary pathology is retinal ganglion cell (RGC) neurodegeneration, not intraocular hypertension.
• Previous neuroprotective strategies, like memantine, have faced clinical trial failures, leading to skepticism.
• The programmed axonal degeneration (PAD) pathway, influenced by nicotinamide mononucleotide (NMN)/NAD+ ratio, presents a new therapeutic target.

Purpose of the Study:

• To re-evaluate the context of neurodegeneration in glaucoma.
• To appraise the pharmacological rationale for NAD+-supporting therapies in glaucoma treatment.

Main Methods:

• Review of clinical evidence on glaucoma pathogenesis.
• Analysis of neuroprotective agent trial outcomes.
• Evaluation of the programmed axonal degeneration (PAD) pathway and NAD+ homeostasis.

Main Results:

• Early RGC neurodegeneration is a critical therapeutic target in glaucoma.
• Skepticism exists regarding neuroprotection due to past trial failures.
• Sustaining axonal NAD+ homeostasis shows promise, with positive proof-of-concept studies.

Conclusions:

• NAD+-supporting therapies offer a novel neuroprotective approach for glaucoma.
• Further clinical trials (Phase 2/3) are underway based on promising preliminary results.
• Contextualizing neurodegeneration and leveraging NAD+ pathways are key for future glaucoma treatments.