Surupa Chakraborty, Amity University Kolkata
Scientists cured lost eyesight in mice by genetically reprogramming the neurons that make up the optic nerve. They used the mice eye as a model tissue to show that the ectopic expression of genes like Oct4, Sox2, and Klf4 (OSK) in mouse retinal ganglion cells can help in restoring vision loss or glaucoma, even in aged mice. The OSK induced genetic reprogramming serves beneficial in axon regeneration after injury, restoration of youthful DNA methylation patterns, and transcriptome studies.
In this recent study, Sinclair and his collaborators aimed at inserting specific genes or reprogramming factors that they have been working with previously for the transformation of adult cells into induced pluripotent stem cells. They chose to work with retinal ganglion cells, which along with axons that make up the optic nerve. The ability to regenerate the optic nerve gets lost with age in mice. To test the novel experimental approach, the scientists crushed the optic nerves of mice with forceps and further injected a harmless viral vector carrying the three reprogramming factors.
As reported by the team in Nature, they minutely observed the DNA methylation patterns and concluded that the injury had resemblances with those in aging mice cells. The treatment was successful as it prevented some damaged retinal ganglion cells from dying and also helped in the regeneration of new functionally active axons.
They carried the same set of experiments on mice with glaucoma and also on mice of middle age. After the final experiments, they concluded that the insertion of reprogramming factors helped in altering the methylation pattern and in gaining back almost about 50% of the lost visual acuity. These data reveal that mammalian tissues behold a record of epigenetics encoded by DNA methylation patterns targeted to restore damaged tissues or cells by in vivo regeneration.
With the successful progress of this therapeutic approach, Sinclair and his company Life Biosciences are planning to test the efficacy and safety of gene therapy in higher model organisms.
Source: EBV-encoded miRNAs regulate type-I IFN response and JAK/STAT signaling pathways
- Reprogramming to recover youthful epigenetic information and restore vision. Yuancheng Lu, Benedikt Brommer, David A. Sinclair, (2020), Nature, Vol. 588, (124-129). https://doi.org/10.1038/s41586-020-2975-4
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