Advancements in Vision Restoration Insights from Zebrafish Photoreceptor Regeneration

Zebrafish can #regenerate retinal cells #after injury, unlike humans. To study whether these regenerated cells function properly, researchers used #two-photon calcium imaging to monitor photoreceptor responses before and after light-induced damage. They focused on #UV cones, which have distinct #responses to different wavelengths of light. Three months after injury, regenerated UV cones regained normal function, responding correctly to both short and long wavelengths. This suggests that stimulating natural regeneration could be a potential strategy for repairing human retinal damage.

Photo source from CRTD: Zebrafish photoreceptor cells stimulated with blue light show correct electrical activity. The picture was taken using the microscope that was custom-built for this study.

Vision relies on the retina, a complex neural tissue at the back of the eye, which is essentially an extension of the brain. Photoreceptor cells in the retina capture light and convert it into electrical signals. In humans, once these photoreceptors are damaged, they do not regenerate, leading to irreversible vision loss.

Researchers, including those at the CRTD in Dresden, are developing therapies to replace damaged photoreceptors and restore vision. These approaches involve either stimulating retinal stem cells to develop into new photoreceptors or transplanting externally grown photoreceptors.

Unlike humans, zebrafish can regenerate parts of their nervous system, including photoreceptors, using stem cells in the retina known as Müller glia. This ability makes zebrafish an ideal model for studying vision restoration.

Prof. Michael Brand, a researcher at CRTD, notes that while human Müller glia cells are similar to those in zebrafish, they have lost their regenerative ability over time. Understanding how zebrafish regenerate photoreceptors could help rekindle this potential in humans.

Previous studies showed that zebrafish regain vision after retinal regeneration, but these tests could not directly measure photoreceptor function. Prof. Brand's team overcame this by using a custom microscope that allowed them to track photoreceptor activity without stimulating the cells unintentionally. Their findings confirmed that regenerated photoreceptors in zebrafish regain full function, responding to light and transmitting signals just like the original cells.

This research offers hope that similar regenerative techniques could eventually be applied to humans, potentially revolutionizing treatments for currently untreatable eye diseases like retinitis pigmentosa and macular degeneration. While clinical application is still far off, this study is a significant step towards that goal.

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Original Source:

Evelyn Abraham, Hella Hartmann, Takeshi Yoshimatsu, Tom Baden, Michael Brand. Restoration of cone-circuit functionality in the regenerating adult zebrafish retina. Developmental Cell, 2024; 59 (16): 2158 DOI: 10.1016/j.devcel.2024.07.005