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Shweta Varshney, Alexandra Petruchenya, German Pinzon-Duarte, Galina Bachay, Gopalan Gnanaguru, Elizabeth Chu, William J. Brunken; Laminin β2 And 3 Are Critical For Retinal Ganglion Cell And Müller Cell Morphogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5432.
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The inner limiting membrane (ILM) is hypothesized to provide trophic environment for the survival and development of retinal ganglion cells (RGCs) and Müller cells (MCs). The β2 and γ3 chains of laminin are important structural components of the retinal ILM. This study investigates the role of β2 and γ3 chains of laminin in the survival, structural development and stability of GCs and MCs.
Retinae from wild type (WT) and β2-/-γ3-/- mice were obtained from PN0 to PN15 and examined by immuno-histochemistry. We also generated mice with EYFP-labeled GCs (Thy1.1-EYFP) on the β2-/-γ3-/- background. In these mice, 10% of GCs are labeled and their arbors could be visualized. Whole-mount preparations from PN15 mice were analyzed; the soma size and dendritic length and area of labeled GCs were measured.
Our previous work has shown that the loss of adhesion to the ILM in the MCs results in MC activation (gliosis), proliferation and sprouting into the vitreous cavity. As MCs are thought to provide trophic support to GCs, in this study we examine the effects of laminin deletion on this cell class. At birth ILM is breached and GCs emerge into the vitreous; this is in stark contrast to WT mice where all of the GCs are confined by the ILM. Using activated caspase 3 marker, we show a progressive loss of GCs in the β2-/-γ3-/- retina during the first two postnatal weeks due to apoptosis. The loss is more prominent in peripheral retina than in central retina. By comparing the EYFP labeled GCs in the PN15 WT and β2-/-γ3-/- retina, a dramatic decrease was observed in the size range of labeled GCs in β2-/-γ3-/- mice. Also a considerable decrease in dendritic area was seen, although the primary and secondary branching pattern of the GCs was less affected. Laminin ablation also leads to optic nerve hypoplasia with defects in axon trajectories and fasciculation. Experiments are currently underway to determine if there is a spatial correlation of MC dysfunction and GC maldevelopment.
Laminin β2 and γ3 chains are critical for the proper development of GCs. Our working hypothesis is this failure is secondary to the disruption of the Müller cell.
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