A recent mouse study from the USC Stem Cell laboratory of Ksenia Gnedeva, Ph.D., has uncovered potential shared genes that could play a crucial role in regenerating cells in both the ear and the eye. Published in the Proceedings of the National Academy of Sciences, the study sheds light on how understanding these genes could lead to advancements in restoring hearing and vision in patients.
According to Gnedeva, the proliferation of progenitor cells in response to injury is essential for the regeneration of sensory receptors. However, this process is often hindered in the inner ear and retina of mammals. By identifying the genes that inhibit this proliferation, researchers can work towards developing strategies to promote regeneration in these vital sensory organs.
The study focused on a group of genes known as the Hippo pathway, which acts as a signal to stop cell growth. The researchers demonstrated that the Hippo pathway not only inhibits cell proliferation during embryonic development but also suppresses the regeneration of damaged sensory receptors in the ear and eye of adult mice.
Using an experimental compound to inhibit a key protein in the Hippo pathway, the researchers observed an increase in the proliferation of supporting cells in the utricle, a sensory organ in the inner ear. However, the same cells did not respond in the organ of Corti, which is responsible for hearing.
Further investigation revealed that a gene encoding a protein called p27Kip1 was blocking the regeneration process in the organ of Corti and was also highly expressed in the retina. By reducing the levels of p27Kip1 in transgenic mice, the researchers were able to stimulate the proliferation of supporting cells in the organ of Corti, a crucial step towards regenerating sensory cells in the ear.
In the retina, inhibiting the Hippo pathway led to the proliferation of progenitor cells known as Müller glia. Interestingly, some of the Müller glia progeny spontaneously converted into sensory photoreceptors and other neuronal cell types in the retina, highlighting the potential for targeted regeneration in the eye.
The study suggests that reducing p27Kip1 levels following injury could create a window of opportunity to inhibit the Hippo pathway and promote regeneration in the ear and eye. These findings open up new possibilities for developing drug-like compounds that target the Hippo pathway and p27Kip1 to stimulate the regeneration of hearing and vision.
Overall, the research provides valuable insights into the genetic mechanisms that regulate cell regeneration in the ear and eye, offering hope for future treatments to restore sensory functions. The study was conducted by a team of researchers from the USC Stem Cell laboratory, including first authors Eva Jahanshir and Juan Llamas. Additional co-authors from the lab contributed to the study, which was supported by the Keck School of Medicine of USC.
For more information, the study titled “The Hippo pathway and p27Kip1 cooperate to suppress mitotic regeneration in the organ of Corti and the retina” can be found in the Proceedings of the National Academy of Sciences.
