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1 From the Department of Structural Pathology, Institute of Nephrology and the 2 Department of Ophthalmology, Faculty of Medicine, Niigata University; the 4 Department of Molecular Interaction and Tissue Engineering Institute for Frontier Medical Sciences, Kyoto University; and the 3 Department of Ophthalmology, Ryukyu University School of Medicine, Naha, Japan.
PURPOSE. To determine the role in the eye of chondromodulin (ChM)-I, which has been identified in cartilage as an angiogenic inhibitor, the expression and localization and a possible function of ChM-I were investigated.
METHODS. Expression and localization of ChM-I in rat eyes were examined by RNase protection assay and in situ hybridization and by immunostaining, using an antibody against a synthetic peptide. The effect of recombinant ChM-I on tube morphogenesis of retinal endothelial cells was examined in culture.
RESULTS. The rat ChM-I gene was determined to encode the open reading frame of
334 amino acid residues, and ChM-I mRNA was exclusively expressed in
cartilage, eye, and cerebellum in rats. ChM-I mRNA expression was
evident in the irisciliary body, retina, and scleral compartments,
but not in other compartments of the eye. In situ hybridization
revealed mRNA expression in the ganglion cells, inner nuclear layer
cells, and pigment epithelium in the retina and in the nonpigment
epithelium of the ciliary body. Immunoreactive ChM-I was present in
these cells and also in the vitreous body. Western blot analysis
detected an
25-kDa band of ChM-I presumed as a secretory form in the
aqueous humor and vitreous body and an
37-kDa band as a precursor
form in the retina. Recombinant human ChM-I inhibited tube
morphogenesis of human retinal endothelial cells in vitro.
CONCLUSIONS. These observations indicate a potential role for ChM-I in inhibition of angiogenesis in the rat eye.
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