Blind Man’s Vision Partially Recovered With Optogenetic Gene Therapy

 

Image Credit: Natali_Mis, et al. “Natali_Mis/Istockphoto.” DallasInnovates.com, Dallas Innovates, 22 June 2021, dallasinnovates.com/bedford-biotech-restores-meaningful-vision-in-blind-patients-with-gene-therapy-and-may-soon-go-public/.

Researchers found with a particular type of gene-based therapy, a man with retinitis pigmentosa gained limited vision. Retinitis pigmentosa is a genetic disease that causes the death of light-gathering cells in the retina of the eyes. The fifty-eight-year-old man was treated with optogenetic therapy, which utilizes a protein sensitive to light and forces the nerve cells to fire off signals when they are struck with a particular light wavelength. Optogenetic therapy is different from conventional gene therapies, which can help to either stop or slow the progression of degenerative eye diseases but do not help those who have already gone blind. 

The researchers, Sahel, Roska, and other team members, used a light protein sensitive to amber light for their clinical trial. The team then used an adeno-associated virus to insert the instructions for making the protein into the ganglion nerve cell layer, which fires messages to the visual parts of the brain. After this treatment, the man was given a pair of goggles that produced amber light pulses to his eyes. With these goggles and the treatment, the man was able to identify objects and count them compared to before the treatment, where he was unable to identify motion or objects. The study team emphasizes that the man needs the goggles to see still as the pulses produced by the goggles make the nerve cells fire off and therefore enables the man to see. While there is only one patient who has shown improvement so far, this progress lays down the foundation for more research on the treatment of degenerative eye diseases. It will help to guide scientists to even better results in the future.

Article Credit: https://www.sciencenews.org/article/blindness-retinitis-pigmentosa-gene-therapy-vision-optogenetics

Link to study: https://www.nature.com/articles/s41591-021-01351-4

Outside the Nucleus: Cytoplasmic DNA Synthesis linked to Degeneration.

        In the article “Human Cells Can Synthesize DNA in Their Cytoplasm” scientists have reports which have identified mammalian DNA to be found in the cytoplasm when they would usually find foreign DNA there. However when complementary DNA (cDNA) was discovered to have been synthesized from RNA scientists were baffled. This is due to the fact that because of the mechanism in which they insert copies of themselves into the genome occurs in a copy and paste pattern where such an event usually occurs in the nucleus. Studying cDNA found in the most abundant retrotransposon Alu, when concerning degenerative eye diseases the cDNA of Alu in humans is found to be synthesized in the cytoplasm. 

        Based on previous studies with Alu and other retrotransposons, the way in which reverse transcription occurs in the nucleus considers that it needs a short nucleic sequence, and primer bound to the RNA template to start. However for Alu to undergo reverse transcription in the cytoplasm the nucleic sequence is not present. Which led to the hypothesis that the RNA folds on itself which is also known as self-priming. The cytoplasmic discovery also correlated that age-related macular degeneration (AMD) is due to the cell death of the retinal pigment epithelium because of the abundance of Alu. Since learning of cDNA synthesized Alu connection to the eye degenerative disease it has also been linked to causing inflammation. To manage AMD scientists developed Alu inhibitors which would control Alu accumulation and even treat other infections. The drug which was developed NRTI is said to prevent inflammation and intercept transcription. Since the current drug is in clinical trial it could help cure a degenerative disease which ultimately leads to permanent blindness. With the development that DNA synthesis can  occur without a nucleic sequence to start transcription it is possible to learn that this mechanism could be responsible for other diseases that currently do not have treatments or most effective treatments.