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New Potential Mechanism for Vision Loss Discovered

Visual cells in the human retina may not simply die in some eye diseases, but are mechanically transported out of the retina beforehand, according to German researchers.

The researchers from the Deutsches Zentrum fur Neurodegenerative Erkrankungen (DZNE) and the Centre for Regenerative Therapies Dresden (CRTD) at TU Dresden made the discovering using organoids, miniature human retinas produced in the laboratory.

The researchers filmed the organoids in real time by so-called live imaging, considered as the gold standard for cell tracking. “We were able to capture the degeneration of photoreceptors through cell extrusion in the lab,” researcher Professor Mike Karl said.

The discovery paves the way for completely new research approaches, especially in connection with age-related macular degeneration (AMD).

That biomechanics may play a larger role in retinal degeneration is a new finding. “

The retina is not known to be a biomechanically active tissue such as a muscle. “It was known that diseases of the nervous system are associated with changes in the shape of cells, but to which extent biomechanical regulators are involved has not yet been studied in detail,” Professor Karl said.

Thanks to the organoids, he and his team were able to observe the processes in an accelerated manner: While it takes several years or even decades for photoreceptors to disappear in patients, the process was reproduced in the laboratory in just 40 days.

In the next step, the researchers now want to find out whether this mechanism occurs in human patients in the same way as in organoids.

Initial findings suggest that this might be the same mechanism, but proof is still lacking.

1. Völkner M., Wagner F., Steinheuer L.M. et al., HBEGF-TNF induce a complex outer retinal pathology with photoreceptor cell extrusion in human organoids. Nature Communications.
Published October 2022. DOI: 10.1038/s41467-022-33848-y