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T. Chiba, J. D. Lindsey, B. T. Gabelt, P. L. Kaufman, R. N. Weinreb; Distribution of Aggrecanase-1 and Aggrecanase-2 in the Primate Uveoscleral Outflow Pathway. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4816.
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Aggrecan is a major proteoglycan in the sclera and may contribute to normal resistance to uveoscleral outflow. Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are enzymes that can cleave specific sites within the aggrecan core protein. Hence, the present study was undertaken to determine the distribution of aggrecanase-1 and aggrecanase-2 in uveoscleral outflow pathway tissues of primate eyes.
Normal cynomolgus monkey eyes (n=3) were fixed informaldehyde, embedded in a modified paraffin, sectioned, and immunostained using specific polyclonal antibodies to aggrecanase-1 and aggrecanase-2. Secondary antibody was conjugated to horseradish peroxidase, immunoreactivity was visualized using diaminobenzidine. The staining within the ciliary muscle, ciliary nonpigmented epithelium, scleral stroma, scleral fibroblasts, blood vessel endothelium and arteriole smooth muscle were evaluated by light microscopy and stain intensity was graded.
Aggrecanase immunoreactivity was observed in each of the eyes throughout the anterior segment. Intense staining for aggrecanase-1 and aggrecanase-2 were observed in ciliary muscle and ciliary nonpigmented epithelium. Light-to-moderate staining for aggrecanase-1 and moderate-to-intense staining for aggrecanase-2 were observed in blood vessel endothelium and arteriole smooth muscle. Light-to-moderate staining for aggrecanase-1 and for aggrecanase-2 were also observed in scleral stroma and scleral fibroblasts. Aggrecanase-2 staining consistently was less in the interior screral stroma than in the exterior screral storoma.
Aggrecanase-1 and aggrecanase-2 were identified in regions of the anterior segment of normal primate eyes which are associated with the uveoscleral outflow pathway. These data indicate that aggrecanase-1 and aggrecanase-2 activity are well-positioned to contribute to the regulation of uveoscleral outflow facility.
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