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Shweta Varshney, Galina Bachay, William J. Brunken; Laminin β2 and 3 chains are critical for retinogenesis and homeostasis of adult retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3963.
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© ARVO (1962-2015); The Authors (2016-present)
Attachment to laminins regulates proliferation, differentiation and survival of cells. The laminin β2 and γ3 chains are important structural components of the inner limiting membrane (ILM) of the retina. This study investigates the role of the laminin β2 and γ3 chains in retinal histogenesis and maintenance of homeostasis in the adult retina.
Retinas collected from postnatal day (P) 0 to 15 wild type (WT) and β2-/-;γ3-/- mice were used for this study. The phenotypes of retinal cells were analyzed by immunohistochemistry using cell specific markers. Gene expression was analyzed using real time PCR and protein expression was analyzed by immunoblots.
Retinal progenitor cells (RPC) and their last progeny, Müller cells (MC), adhere to the ILM at their basal surface. Our data suggest that deletion of Lamb2 and Lamc3 leads to disruption of the ILM as early as P0. Concurrent with the ILM disruption, retinal cells lose two key laminin receptors: β-dystroglycan and β1-integrin. In tandem with this disruption, RPCs proliferate abnormally. In the P0 β2-/-;γ3-/- retina, proliferation assessed using markers such as phosH3 and PCNA is increased compared to WT; in contrast, by P5 in the β2-/-;γ3-/- retina, the rate of proliferation declines by 1.5 fold compared to WT. The changes in proliferation in the β2-/-;γ3-/- retina suggest changes in retinogenesis, consistent with our previous report of the presence of rosettes in the P15 β2-/-;γ3-/- retina. Experiments are currently underway to evaluate the precise changes in cell fate specification corresponding with the changes in proliferation in the β2-/-;γ3-/- retina. Additionally, in MC of the P15 β2-/-;γ3-/- retina, GFAP expression is increased, indicating gliosis, whereas Kir4.1 and Aqp4 channel expression are decreased, indicating dysregulation in ion homeostasis and MC hypertrophy. These changes in MCs are also accompanied by remodeling of the second and third order neurons.
These data suggest that interactions of RPCs and MCs with the ILM play important roles in retinal histogenesis and help to maintain normal cellular architecture, promoting functional stability in the adult retina.
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