Joel S. Schuman教授：维持／恢复视网膜神经元功能，这些方向大有前景！

▍滑动查看英文原文

Glaucoma is the most common irreversible blinding condition. To date, our treatments have focused entirely on lowering intraocular pressure, which is crucial but likely not the full story. Various compounds have been tested for neuroprotection, neuroenhancement, or neuroregeneration, though none are currently FDA-approved in the U.S. for these purposes. Evidence suggests that nicotinamide and pyruvate can be neuroprotective. These would be used alongside intraocular pressure-lowering treatments. A second study, likely conducted at Columbia University, is examining the combination of these supplements for neuroprotection. Other agents like citicoline, turmeric (curcumin), and resveratrol(found in wine) have been investigated for neuroprotective properties. While they show potential, the evidence supporting their efficacy is less robust compared to intraocular pressure-lowering therapies. Among these, nicotinamide and pyruvate have the strongest evidence base.Several drugs are under investigation for neuroprotection. For instance, Nerve Growth Factor (NGF) might provide neuroprotection or even neuroenhancement—improving the function of existing neurons without regenerating new ones. Studies presented at the American Academy of Ophthalmology have explored CNTF (Ciliary Neurotrophic Factor) for similar purposes. Additionally, a molecule being developed blocks endothelin-1A, potentially improving structural and functional outcomes in glaucoma patients. This falls under the category of neuroenhancement. Other promising agents are also in the research pipeline.

▍滑动查看英文原文

Yes, I mentioned nicotinamide (vitamin B3) and pyruvate, which are believed to reduce inflammation and support cell health. Other antioxidants, such as resveratrol, and nerve-enhancing drugs like citicoline and turmeric, have also been studied. NGF and CNTF promote neuron health, while endothelin-1 antagonists work through a completely different mechanism. Endothelin is the body’s most potent vasoconstrictor, and blocking it enhances blood flow to the retina. This increased blood flow provides better nutrition, removes waste, and appears to improve visual function, as demonstrated in phase II studies involving intravitreal administration. While these agents do not regenerate neurons, they enhance the functionality of existing ones. Other drugs with varying mechanisms are also in development, though at earlier stages in the pipeline.

▍滑动查看英文原文

This research focuses on regeneration. Our consortium, including Yi Chin, Du Dan Stamer, Ross Ether, and myself, published a paper in *Progress in Retinal and Eye Research* on this topic. We have used various stem cell types—adipose-derived, embryonic, and pluripotent—injecting them into the anterior chamber of mice with laser-induced glaucoma. These cells successfully rebuilt the trabecular meshwork, restoring both its structure and function. We’ve observed that stem cells seem to target the trabecular meshwork, possibly through chemotactic signals or due to fluid dynamics. Interestingly, when fibroblasts are used instead, they distribute randomly rather than targeting the trabecular meshwork. It's unclear whether stem cells transform into trabecular meshwork cells or release factors that enhance the function of existing cells. Similar uncertainties exist with other uses of stem cells in the body. Our experiments have progressed from mice to larger animals like pigs. Human trials, however, require significant resources and regulatory approvals to ensure safety. We are working to secure the necessary support for these next steps.

▍滑动查看英文原文

The areas I’ve mentioned remain hot topics and require further investigation. One area I haven’t discussed is artificial intelligence (AI), particularly its application to imaging analytics and medical data. Imagine examining a patient for the first time, taking a fundus photo, and determining with high certainty whether they are healthy or have a condition like glaucoma, diabetic retinopathy, or macular degeneration. AI could significantly enhance screening, especially in areas with limited access to care. AI could also monitor disease progression and predict its trajectory, helping physicians tailor care. For example, it could indicate whether a patient needs follow-up in one month or two years. This would reduce the burden on both patients and healthcare systems. By incorporating data from fundus images, OCT, visual fields, and medical records, AI has the potential to provide even more precise diagnostics. Large language models and other AI algorithms are at the forefront of this field, which I find incredibly exciting.

▍滑动查看英文原文

Currently, there’s enough uncertainty around algorithm outputs that most physicians would prefer to review the data themselves. It’s essential to ensure that the AI’s conclusions are understandable and logical. That said, we are already using autonomous AI for diabetic retinopathy screening, and similar applications for referable glaucoma are on the horizon. Over time, I believe we will grow to trust AI more and use it independently for diagnostics.