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L. Cammas, J. Wolfe, S. Y. Choi, S. Dedhar, H. Beggs; Integrin-Linked Kinase (ilk) is Critical for Stability of the Lens Capsule Extracellular Matrix and for Survival of Lens Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2357.
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© ARVO (1962-2015); The Authors (2016-present)
Integrin-mediated signaling between the cell and its environment critically directs many aspects of development and is frequently disrupted in disease. The lens epithelium and its interaction with the lens capsule basement membrane is an effective model system to study integrin-mediated signaling in an in vivo, tissue context. To gain insight into how integrin mediated signaling impacts lens development, we have specifically deleted Integrin-Linked Kinase (ILK) from the lens at different stages. ILK is a key component of the integrin cell-matrix signaling pathway, and is also responsive to growth factor signaling pathways, but its function in the lens remains poorly understood.
Conditional deletion of ILK in the lens was accomplished at either early (E9.5) or later stages (E12.5) of lens development using LE-Cre and Nestin-Cre mouse lines. In parallel, epithelial explants were generated from the ILK-floxed newborn lenses and subjected to ILK deletion in culture via adenovirus infection with adeno-Cre-eGFP. Samples were analyzed using histological and biochemical methods.
Early deletion of ILK leads to lens epithelial disorganization and matrix defects. The capsule is unable to properly close upon separation of the lens vesicle from the surface ectoderm, leading to anterior capsule rupture and epithelial cell death by E14.5. In lenses where ILK is deleted at later stages, the capsule is able to form but becomes thin and uneven. Importantly, the central epithelial cells die by E17.5 leaving the anterior lens acellular. As a secondary defect, anterior endfeet of the lens fibers fail to migrate along the epithelial-fiber interface creating a bowed morphology, whereas the posterior endfeet show no abnormalities. Lens explants containing epithelial cells attached to the capsule were used to study the effect of ILK deletion on extracellular matrix formation and organization as well as the response to cell survival cues.
Those results identify a critical role for ILK in lens capsule development and in epithelial cell survival.
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