NeuroD1-Mediated Gene Therapy Restores Cortical Connectivity & Visual Function in Mice after Stroke

Article: Gene therapy can restore vision after stroke
Source: Purdue University
Published: September 28, 2021

Reprogrammed cells (orange) are integrated into the
microcircuit and hyper-connected at an early stage

Strokes happen when blood flow to neural tissue stops, leading to neuronal loss and gliosis. A large portion of the cerebrum is devoted to processing vision, thus when an artery is blocked in these regions, vision loss can result. Researchers are exploring the use of gene therapy to directly reprogram endogenous astrocytes into neurons in situ as a means to restore vision in the aftermath of irreversible death of neurons. As compared to the plasticity found when the brain remaps its pathways, a slow and inefficient process, the new gene therapy offers a more efficient solution. The technique shows promise thus far in a model of ischemic stroke affecting the visual centers in the brains of mice, in particular using adeno-associated viruses to deliver transcription factor NeuroD1 in vivo to glial cells in the affected area of the brain. These cells were observed to reprogram into neurons and integrate into the microcircuits of the visual cortex. Furthermore, following visual experience, the reprogrammed neurons demonstrated maturation of orientation selectivity and functional connectivity. One of the researchers comments, “We don’t have to implant new cells, so there’s no immunogenic rejection. This process is easier to do than stem cell therapy, and there’s less damage to the brain. We are helping the brain heal itself. We can see the connections between the old neurons and the newly reprogrammed neurons get reestablished. We can watch the mice get their vision back.” They conclude, "Our results show that NeuroD1-reprogrammed neurons can successfully develop and integrate into the visual cortical circuit leading to vision recovery after ischemic injury." The researchers hope that the techniques they develop to restore function in the visual cortex will then help in perfecting techniques to restore motor function after stroke.

My rating of this study: ⭐⭐

Tang Y, Wu Q, Gao M, et al. "Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy." Frontiers in Cell and Developmental Biology.  18 August 2021. https://doi.org/10.3389/fcell.2021.720078