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The Ophthalmologist / Issues / 2023 / Mar / All Molecules Great and Small
Neuro-ophthalmology Research & Innovations Glaucoma

All Molecules Great and Small

Stimulating nerve regeneration and restoring visual functions after optic nerve injury with M1 – a small molecule drug

By Sarah Healey 3/9/2023 2 min read

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Credit: Images used sourced from Shutterstock.com and Pixabay.com

A “research breakthrough” from a team at the City University of Hong Kong (CityU) “heralds a new approach that could address unmet medical needs in accelerating functional recovery within a limited therapeutic time window after CNS injuries (1).” Specifically, the researchers have shown how a small molecule, called M1, can stimulate nerve regeneration and restore visual function in an optic nerve crush (ONC) mouse model. The researchers demonstrated that M1 works by increasing the fusion and motility of mitochondria, which stimulates sustained, long-distance axon regeneration (2).

We asked Eddie Ma Chi-him – Associate Head and Associate Professor in the Department of Neuroscience and Director of the Laboratory Animal Research Unit at CityU and lead researcher – to provide some context: “Our research exemplifies the importance of mitochondria-based approaches in enhancing axon regeneration and function recovery after CNS injury. To this end, clinically approved drugs that modulate mitochondria function can be repurposed to treat CNS injury and glaucoma-related vision loss diseases, saving both time and money.”

How did the team get there? In short, the researchers assessed axon regeneration in M1-treated mice four weeks post injury; notably, no regeneration was found in vehicle-treated control mice, but axon regeneration in M1-treated mice reached a striking 4 mm distal to the crush site. Additionally, the survival of retinal ganglion cells in M1-treated mice increased from 19 percent to 33 percent post injury.

To further explore the efficacy of M1 treatment for visual restoration, the research team challenged the M1-treated mice with a pupillary light reflex test six weeks post injury. The results showed that, upon blue light illumination, the lesioned eyes of M1-treated mice restored pupil constriction response to a similar extent of the non-lesioned eyes, indicating that M1 treatment can rescue pupil constriction response after ONC injuries.

The work builds on the team’s previous research, which used gene therapy to stimulate peripheral nerve regeneration – but, as aforementioned by Chi-him, the latest research highlights the potential of a readily available and non-viral therapy for repair. In light of the promising findings, the team are currently developing an animal model to assess the efficacy of M1 in treating glaucoma-related vision loss, with the potential to expand into other conditions, including diabetic retinopathy, macular degeneration, and traumatic optic neuropathy.

References

  1. CityU, “Small molecule identified by CityU researchers offers great therapeutic potential for restoring vision” (2023). Available at: http://bit.ly/41UJuFz. 
  2. N P B Au et al., “A small molecule M1 promotes optic nerve regeneration to restore target-specific neural activity and visual function,” Proceedings of the National Academy of Sciences, 199, (2022). PMID: 36306327.

About the Author(s)

Sarah Healey

Communicating stories in a way that is accessible to all was one of the focal points of my Creative Writing degree. Although writing magical realism is a fun endeavor (and one I still dabble in), getting to the heart of human stories has always been the driving motivator behind my writing. At Texere, I am able to connect with the people behind scientific breakthroughs and share their stories in a way that is impactful and engaging.

More Articles by Sarah Healey

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