Laminin γ3 plays an important role in retinal lamination, photoreceptor organisation and ganglion cell differentiation

Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin alpha 1, alpha 5, beta 1, beta 2 and gamma 1 to be predominantly expressed in Bruch's membrane and the inner limiting membrane. Laminin-332 and laminin gamma 3 expression were mainly observed in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin gamma 3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organisation and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin gamma 3 during human retinogenesis.