Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina

Astrocytes regulate retinal vascular development. Generated extrinsically to the retina, astrocytes migrate into the retina through the optic nerve head. In this study, we show that astrocytes migrate within a laminin-containing basement membrane. Genetic deletion of the laminin β2 and γ3 chains affects astrocyte migration and spatial distribution. We show that laminins act as haptotactic factors in vitro in an isoform-specific manner, inducing astrocyte migration and promoting astrocyte differentiation. The addition of exogenous laminins to laminin-null retinal explants rescues astrocyte migration and spatial patterning. Furthermore, we show that the loss of laminins reduces β1 integrin expression in astrocytes which can be restored when astrocytes are cultured on Biolaminin 521 or Matrigel. Finally, they show that laminins containing β2 and γ3 chains regulate subsequent retinal blood vessel growth and maintain vascular integrity. These in vivo and in vitro studies demonstrate clearly that laminins containing β2 and γ3 chains are indispensable for migration and spatial organization of astrocytes and that they play a crucial role during retinal angiogenesis in vivo.