Defective Formation of the Inner Limiting Membrane in Laminin β2-and γ3-Null Mice Produces Retinal Dysplasia

PURPOSE. Retinal basement membranes (BMs) serve as attachment sites for retinal pigment epithelial cells on Bruch's membrane and Muller cells (MCs) on the inner limiting membrane (ILM), providing polarity cues to adherent cells. The beta 2 and gamma 3 chains of laminin are key components of retinal BMs throughout development, suggesting that they play key roles in retinal histogenesis. This study was conducted to analyze how the absence of both beta 2- and gamma 3-containing laminins affects retinal development. METHODS. The function of the beta 2- and gamma 3-containing laminins was tested by producing a compound deletion of both the beta 2 and the gamma 3 laminin genes in the mouse and assaying the effect on postnatal retinal development by using anatomic and electrophysiological techniques. RESULTS. Despite the widespread expression of beta 2 and gamma 3 laminin chains in wild-type (WT) retinal BMs, the development of only one, the ILM, was disrupted. The postnatal consequence of the ILM disruption was an alteration of MC attachment and a resultant disruption in MC apical-basal polarity, which culminated in retinal dysplasia. Of importance, although their density was altered, retinal cell fates were unaffected. The laminin mutants have a markedly decreased visual function, resulting in part from photoreceptor dysgenesis. CONCLUSIONS. These data suggest that beta 2 and gamma 3 laminin isoforms are critical for the formation and stability of the ILM. These data also suggest that attachment of the MC to the ILM provides important polarity cues to the MC and for postnatal retinal histogenesis. (Invest Ophthalmol Vis Sci. 2010;51:1773-1782) DOI:10.1167/iovs.09-4645