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N. Gupta, K. Fung, A. Proia; The Effects of Calcipotriol, a Synthetic Vitamin D3 Analog, on Corneal Angiogenesis Induced in the Rat . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4477.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The active metabolic form of vitamin D3, 1α,25–(dihydroxy)–vitamin D3, decreases the angiogenic response to tumor cells in several in vivo and in vitro models. We evaluated the ability of topical calcipotriol, a Vitamin D3 analog, to inhibit corneal neovascularization induced in the rat by silver nitrate cauterization. Methods: Following corneal injury, 42 rats were randomized into six groups (N=7) and were given either control vehicle or topical calcipotriol for four days. 30µl of topical calcipotriol was applied four times per day in vehicle (carbopol, thimerosal, mannitol) at concentrations of 0.1, 1, 10, 50, or 100 µg/ml. Upon completion of the treatment period, the rats were perfused with India ink–gelatin solution intravenously. The corneas were harvested and mounted on a glass slide. A masked observer utilized digital computer image analysis to measure the amount of angiogenesis in mm/mm2 of corneal area. Results: The findings are expressed as the mean ± 1 SEM for total length of vessels (in mm) per mm2 of corneal area for each treatment group. Inhibition of corneal neovascularization by increasing concentrations of topical calcipotriol was not statistically significant (P>0.05) when compared to the vehicle–treated group. Topical vehicle demonstrated 11.1 ± 1.33mm/mm2 of corneal angiogenesis. While 0.1 µg/ml of calcipotriol demonstrated 14.3 ± 0.75mm/mm2; 1 µg/ml of calcipotriol displayed 11.2 ± 1.26mm/mm2; 10 µg/ml of calcipotriol demonstrated 11.9 ± 0.98mm/mm2; 50 µg/ml of calcipotriol displayed 15.1 ± 0.30mm/mm2; and 100 µg/ml of calcipotriol demonstrated 12.6 ± 0.77mm/mm2 of corneal neovascularization, respectively. Conclusions: Our results do not support a role for the Vitamin D3 analog, calcipotriol, as a therapeutic agent in the treatment for corneal neovascularization induced by the severe injury utilized in this study. This may reflect different responses of tumor and corneal angiogenesis or differing binding affinities for calcipotriol and other vitamin D3 derivatives for receptors associated with angiogenesis.
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