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Updated: Jun 24, 2026
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Optic Nerve Transection: A Model of Adult Neuron Apoptosis in the Central Nervous System
Published on: May 12, 2011
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Programmed axon death: a promising target for treating retinal and optic nerve disorders
Andrea Loreto1,2, Elisa Merlini3, Michael P Coleman4
1John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Robinson Way, Cambridge, UK. andrea.loreto@sydney.edu.au.
Eye (London, England)
|March 28, 2024
Summary
Programmed axon death, involving NMNAT2 and SARM1 enzymes, offers a druggable target for neurodegenerative diseases. Targeting this pathway shows significant neuroprotection in preclinical models, advancing toward clinical trials for eye disorders.
Area of Science:
- Neuroscience
- Pharmacology
- Ophthalmology
Background:
- Programmed axon death is a key pathway in neurodegeneration, with enzymes NMNAT2 and SARM1 central to NAD metabolism.
- This pathway is a significant therapeutic target for pharmaceutical companies in neurodegenerative disorders.
Purpose of the Study:
- To review mechanisms of programmed axon death in the retina and optic nerve.
- To discuss the therapeutic potential for eye disorders and beyond, including roles of SARM1 and NAD metabolism.
Main Methods:
- Review of preclinical data in disease models.
- Analysis of genetic human data and environmental triggers.
- Discussion of therapeutic approaches targeting NMNATs and SARM1, and nicotinamide trials.
Main Results:
- Preclinical data show remarkable neuroprotection when programmed axon death is targeted.
- Genetic human data are beginning to substantiate animal study findings, supporting clinical translation.
- The eye's suitability for drug delivery and assessment makes retinal disorders strong candidates for trials.
Conclusions:
- Targeting programmed axon death presents a promising therapeutic strategy for neurodegenerative conditions.
- Retinal and optic nerve disorders are prime candidates for early clinical trials due to existing evidence and practical advantages.
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