Regulation of Adult Zebrafish Retinal Regeneration by Lamβ1b-Chain-Containing Laminins

Retinal degenerative diseases are a major cause of blindness in humans that often result in permanent and progressive loss of vision. Unlike humans, zebrafish possess the remarkable ability to regenerate lost retinal neurons through Müller glia (MG) reprogramming and asymmetric cell division to produce multipotent retinal progenitor cells (RPCs). While most studies on the molecular mechanisms underlying this regeneration process have focused on intracellular mechanisms, the role of the microenvironment surrounding retinal cells, the extracellular matrix (ECM), has been understudied. Laminins are heterotrimeric glycoproteins, are principal components of the ECM basement membrane, and play important roles in vertebrate retinal development. Here, we examine the role of β1b chain-containing laminins in the regenerative response of the zebrafish retina. We found that the zebrafish lamb1b gene is differentially expressed during MG reprogramming and MG and NPC proliferation during retinal regeneration. Further, we found that β1b-containing laminins play important roles in regulating MG and NPC proliferation and neuroprotection of photoreceptors in light-damaged zebrafish retinas. Finally, Lamβ1b plays an important role in regulating the expression of integrin receptors and other laminin genes during the regeneration response. Taken together, Lamβ1b, and likely other ECM components, play a critical role in the MG-dependent neuronal regeneration response in the zebrafish retina.