title: Laminins containing the β2 and γ3 chains regulate astrocyte migration and angiogenesis in the retina.
abstract: Pathologies of retinal blood vessels are among the major causes of blindness worldwide. A key cell type that regulates retinal vascular development is the astrocyte. Generated extrinsically to the retina, astrocytes migrate into the retina through the optic nerve head. Even though there is a strong correlation between astrocyte distribution and retinal vascular development, the factors that guide astrocytes into the retina remain unclear. In this study, we show that astrocytes migrate within a laminin-containing basement membrane - the inner limiting 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. Culturing laminin-null retinal astrocytes on laminin substrates restores focal localization of β1 integrin. Finally, we 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.
authors.affiliation: Departments of Ophthalmology and Cell Biology, and the SUNY Eye Institute, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
authors.forename: Gopalan
authors.initials: G
authors.lastname: Gnanaguru
authors.forename: Galina
authors.initials: G
authors.lastname: Bachay
authors.forename: Saptarshi
authors.initials: S
authors.lastname: Biswas
authors.forename: Germán
authors.initials: G
authors.lastname: Pinzón-Duarte
authors.forename: Dale D
authors.initials: DD
authors.lastname: Hunter
authors.forename: William J
authors.initials: WJ
authors.lastname: Brunken
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D016510:Corneal Neovascularization / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000378:metabolism
chemical_list: D019012:Integrin beta1; C504220:Lamc3 protein, mouse; D007797:Laminin; D017474:Receptors, Laminin; C058783:laminin beta2