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D. R. Lazzaro, Y. Li, G. A. Pinzón-Duarte, A. Lee, R. Pointdujour, P. Chamnongvongse, R. T. Libby, W. J. Brunken; Anterior Segment Disruptions in Laminin and Netrin Null Mice: Pierson Syndrome and Beyond. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2587.
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Basement membranes (BMs) are important in anterior segment development and disease. Mutations of the laminin β2 gene in humans cause Pierson's syndrome, a nephritic disease with ocular abnormalities. Using conventional knockout technology, we have examined the function of several basement membrane components in the anterior segment.
Eyes from age-matched wild type (WT), netrin-4 -/-, laminin β2-/-, laminin γ3-/-, and laminin β2-/-;γ3-/- mice were examined by conventional histology and IHC.
Netrin-4 is expressed in: the ILM and Bruch's membrane; the BMs of the ciliary body and iris; the anterior and posterior lens capsule. In the cornea, netrin-4 is in Bowman's membrane, the stromal matrix and Descemet's membrane; there is no expression in the sclera. Laminin β2 and γ3 follow the same expression pattern with the exception that γ3 is more limited in distribution. Eyes of netrin-4 null mouse were well formed. However, the cornea was thickened with an increased proliferation of the epithelial cells but not the endothelial or stromal cells. Interestingly, mitotic cells were found among the apical cells of the cornea consistent with rapid turnover of corneal epithelium. The eyes of the laminin β2 and β2γ3 nulls were reduced in size. The corneas of the β2 and β2γ3 null mice were thicker than WT mice, possibly due to stromal swelling. Proliferation of the corneal epithelium was increased in the β2 null mice; however, there was an increased density in the corneal endothelium as well. Finally, laminin β2 and β2γ3 null animals showed evidence of posterior synechia and ciliary body disruptions and pars plana dysgenesis.
These data demonstrate that laminins and netrin-4 are critical components of ocular development, particularly for cornea development. Additional studies are underway to determine the molecular mechanisms of corneal regulation and the role of these molecules in wound healing. Furthermore, the laminins appear to have an important role in most of the structures of the anterior segment.
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