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T. Chiba, J. D. Lindsey, K. N. Wright, B. T. Gabelt, P. L. Kaufman, R. N. Weinreb; Distribution of Aggrecanase-1 and Aggrecanase-2 in the Primate Retina and Optic Nerve Head. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3690.
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Aggrecan is the largest proteoglycan within extracellular matrix of the sclera (Rada. JA et al. IOVS. 1997) and lamina cribrosa (Morrison JC. Trans Am Ophth Soc. 2006). Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are enzymes that can cleave specific sites within the aggrecan core protein and other proteoglycans. Hence, the present study was undertaken to determine the distribution of aggrecanase-1 and aggrecanase-2 in optic nerve head as well as retina tissues.
Normal cynomolgus monkey eyes (n=4) were fixed in formaldehyde, 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 and immunoreactivity was visualized using diaminobenzidine. The staining within the retina, choroid, posterior sclera, optic nerve axon bundles, glia and lamina beams were evaluated by light microscopy and stain intensity was graded.
Aggrecanase immunoreactivity was observed in each of the eyes throughout the most of neural retinal layer and the optic nerve head. Intense staining for aggrecanase-1 and light-to-moderate staining for aggrecanase-2 was observed in nerve fiver layer and optic nerve axon bundle. Variable staining for aggrecanase-1 and aggrecanase-2 was observed in other retinal layers. No staining for aggrecanase-1 and aggrecanase-2 was observed in retinal pigment epithelium and choroid. Light staining for aggrecanase-1 and aggrecanase-2 was observed in posterior sclera and laminar beams. Moderate-to-intense staining for aggrecanase-1 and aggrecanase-2 was observed in optic nerve head glia. (Table 1)
These data indicate that aggrecanase-1 and aggrecanase-2 activity are well-positioned to contribute to the physiological regulation of proteoglycans in the optic nerve head and retina.
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