Cellular and Molecular Triggers of Retinal Regeneration in Amphibians

Understanding the mechanisms triggering the initiation of retinal regeneration in amphibians may advance the quest for prevention and treatment options for degenerating human retina diseases. Natural retinal regeneration in amphibians requires two cell sources, namely retinal pigment epithelium (RPE) and ciliary marginal zone. The disruption of RPE interaction with photoreceptors through surgery or injury triggers local and systemic responses for retinal protection. In mammals, disease-induced damage to the retina results in the shutdown of the function, cellular or oxidative stress, pronounced immune response, cell death and retinal degeneration. In contrast to retinal pathology in mammals, regenerative responses in amphibians have taxon-specific features ensuring efficient regeneration. These include rapid hemostasis, the recruitment of cells and factors of endogenous defense systems, activities of the immature immune system, high cell viability, and the efficiency of the extracellular matrix, cytoskeleton, and cell surface remodeling. These reactions are controlled by specific signaling pathways, transcription factors, and the epigenome, which are insufficiently studied. This review provides a summary of the mechanisms initiating retinal regeneration in amphibians and reveals its features collectively directed at recruiting universal responses to trauma to activate the cell sources of retinal regeneration. This study of the integrated molecular network of these processes is a prospect for future research in demand biomedicine.