About this Research Topic
Retinal degenerative diseases and traumatic injury result in permanent loss of retinal neurons and thus sight, depriving many worldwide of one of our most valued senses. Due to the clinical need for sight preservation or restoration, a variety of therapeutic methods are currently being investigated for efficacy in either delaying, halting, or even reversing the loss of retinal neurons. By far, the most active area of research in vision preservation and restoration is in retinal regenerative medicine, which aims to replace defective or lost photoreceptors, ganglion cells, or retinal pigment epithelium. Currently, such approaches are focused on either cell replacement therapy via a donor population or reprogramming of endogenous cellular sources into new retinal neurons.
Advancements in mouse and human induced pluripotent stem cell (iPSC) technology and retinal organoid culture have made significant advances in deriving candidate cells for transplantation. There are also claims that adeno-associated virus mediated gene transduction of reprogramming factors is capable of forcing endogenous mouse Müller glial cells into a progenitor cell-like state capable of neurogenesis. While a significant number of these studies report some improvement of mouse retinal disease models, few have conclusively demonstrated integration of new retinal neurons into the pre-existing retinal circuitry. It is likely that these studies have yet to fully address the ability of transplanted or reprogrammed cells to survive in a diseased or damaged retinal environment, migrate to the proper location, undergo a normal terminal differentiation program, and synapse with the appropriate partners. While understanding these fundamental processes may seem daunting, the zebrafish retina may hold the answers as it has an amazing ability to undergo Müller glial cell-mediated regeneration of all retinal neurons, which are able to functionally integrate and restore vision.
This Research Topic is intended to foster the exchange of ideas aimed at achieving robust retinal regeneration therapies capable of conferring vision to individuals with retinal disease. We highly encourage comparative, mechanistic studies between the mouse and the regenerative zebrafish retina. We are also interested in newer ideas related to artificial bypass of the retina altogether using strategies such as optogenetic prosthesis and bionic retinal implants. Special emphasis will be placed, but is not limited to the following areas:
• Fundamental cellular, molecular, genetic, and epigenetic mechanisms of Müller glial cell-mediated retinal regeneration or its prevention in mammals.
• Injury-induced dedifferentiation and acquisition of neurogenic competence in Müller glia and RPE of non-mammalian vertebrates.
• Promotion of survival and integration of transplanted or regenerated retinal neurons.
• The role of changes in the extracellular matrix and/or biomechanical forces in response to retinal damage or during regeneration.
• Development of new animal pre-clinical models of retinal dystrophy.
• New adeno-associated virus strategies to promote retinal reprogramming or transdifferentiation.
Keywords: Müller glia, Retinal regeneration, Retinal degenerative disease, Therapeutic strategy, Retinal dystrophy, Zebrafish, Retinal disease, Optogenetics, Neurogenesis
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