Defective formation of the inner limiting membrane in laminin beta2- and gamma3-null mice produces retinal dysplasia.
Retinal basement membranes (BMs) serve as attachment sites for retinal pigment epithelial cells on Bruch's membrane and Müller cells (MCs) on the inner limiting membrane (ILM), providing polarity cues to adherent cells. The beta2 and gamma3 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 beta2- and gamma3-containing laminins affects retinal development. Methods. The function of the beta2- and gamma3-containing laminins was tested by producing a compound deletion of both the beta2 and the gamma3 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 beta2 and gamma3 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 beta2 and gamma3 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.
Pinzón-Duarte
Germán
G
Department of Cell Biology, 4Ophthalmology, StateUniversity of New York, Downstate Medical Center, Brooklyn, NewYork 11203, USA.
Daly
Gerard
G
Li
Yong N
YN
Koch
Manuel
M
Brunken
William J
WJ
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western; D002454:Cell Differentiation; D003623:Dark Adaptation; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D017353:Gene Deletion; D005838:Genotype; D007150:Immunohistochemistry; D007797:Laminin / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure; D015792:Retinal Dysplasia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
C504220:Lamc3 protein, mouse; D007797:Laminin; C058783:laminin beta2