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Journal of Histochemistry and Cytochemistry, Vol. 51, 503-511, April 2003, Copyright © 2003, The Histochemical Society, Inc.

ARTICLE

Expression of the Matricellular Protein SPARC in Murine Lens: SPARC Is Necessary for the Structural Integrity of the Capsular Basement Membrane

Qi Yana, David Blakea, John I. Clarkb, and E. Helene Sagea
a Department of Vascular Biology, The Hope Heart Institute, Seattle, Washington
b Departments of Biological Structure & Ophthalmology, University of Washington, Seattle, Washington

Correspondence to: E. Helene Sage, Dept. of Vascular Biology, Hope Heart Institute, 1124 Columbia Street, Suite 720, Seattle, WA 98104. E-mail: hsage@hopeheart.org

SPARC (Secreted Protein, Acidic and Rich in Cysteine) is a matricellular glycoprotein that modulates cell proliferation, adhesion, migration, and extracellular matrix (ECM) production. Although SPARC is generally abundant in embryonic tissues and is diminished in adults, we have found that the expression of SPARC in murine lens persists throughout embryogenesis and adulthood. Our previous studies showed that targeted ablation of the SPARC gene in mice results in cataract formation, a pathology attributed partially to an abnormal lens capsule. Here we provide evidence that SPARC is not a structural component of the lens capsule. In contrast, SPARC is abundant in lens epithelial cells, and newly differentiated fiber cells, with stable expression in wild-type mice up to 2 years of age. Pertubation of the lens capsule in animals lacking SPARC appears to be a consequence of the invasion of the lens cells situated beneath the capsule. Immunoreactivity for SPARC in the lens cells was uneven, with minimal reactivity in the epithelial cells immediately anterior to the equator. These epithelial cells appeared essentially noninvasive in SPARC-null mice, in comparison to the centrally located anterior epithelial cells, in which strong labeling by anti-SPARC IgG was observed. The posterior lens fibers exhibited cytoplasmic extensions into the posterior lens capsule, which was severely damaged in SPARC-null lenses. The expression of SPARC in wild-type lens cells, together with the abnormal lens capsule in SPARC-null mice, indicated that the structural integrity of the lens capsule is dependent on the matricellular protein SPARC. The effects of SPARC in the lens appear to involve regulation of lens epithelial and fiber cell morphology and functions rather than deposition as a structural component of the lens capsule. (J Histochem Cytochem 51:503–511, 2003)

Key Words: SPARC, basement membrane, lens capsule, lens epithelial cells, lens fiber cells, collagen type IV, ß1 integrin, matricellular protein


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