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Y.-S. Bee, S.-J. Sheu, J.-C. L. Lin, H.-C. Lin, M.-H. Tai; Topical Application of Vasotatin48 Attenuates the Development of Choroidal Neovascularization in Rats Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1773.
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Vasostatin 48 (VS48) is a peptide fragment derived from residues 133-180 of calreticulin. This study was designed to investigate the effects of topical application of recombinant VS48 on experimental choroidal neovascularization (CNV).
Recombinant VS48 was expressed and purified as thioredoxin (TRX)-fused protein. CNV was induced in Brown Norway rats by fundus Argon laser photocoagulation and evaluated by fundus fluorescein angiography (FAG). One day after CNV induction, the rats were either left untreated or treated with topical application of eye-drop containing TRX or TRX-VS48 (final concentration of 1 µg/ml; n = 12) three times daily for 20 days. The CNV extents in different groups of rats were evaluated by FAG on day 21, 28, 35 and 42. The effect and safety of topical VS48 application on retina function were examined by electroretinography (ERG) on day 42. After the final round of FAG and ERG analysis, the CNV in rat eyes were subjected to hematoxylin-eosin (H&E) staining and immunohistochemical analysis using antibodies against von Willebrand's factor (vWF).
FAG analysis revealed that the eyes received topical VS48 exhibited significant decrease in CNV lesion areas compared with untreated or TRX-treated eyes on day 21, 28, 35 and 42 (P < 0.05). This was consistent with histological findings, which revealed a significant reduction in CNV lesions and number of vWF-positive blood vessels in VS48-treated choroidal tissues. In ERG analysis, CNV lesion induced a prolonged latency in a- and b-wave. Topical application VS48, but not TRX, significantly shorten the delayed a wave and b wave due to CNV (P < 0.05). Finally, there was no difference in ERG parameters between normal and VS48-treated rats eyes, suggesting that the safety of VS48.
The present study demonstrates the potential of topical VS48 application to ameliorate choroidal neovascularization.
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