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B. H. Bakir, M. d. Cano, E. D. Karagiannis, M. S. Soliman, A. S. Popel, P. L. Gehlbach; Peptides Derived From Thrombospondin Type 1 Domain-Containing Proteins Inhibit Corneal Neovascularization in vivo. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4596.
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The cornea is normally an avascular and optically transparent tissue. Corneal neovascularization is a frequent complication of eye disease in the U.S. and world. Hypoxia, inflammation, infection, chemical burns and trauma all contribute to neovascularization of the cornea. Vasogenic factors such as b-FGF, interleukins, and VEGF mediate vascular formation. Without effective treatment, corneal neovascularization can lead to corneal opacity and severe vision loss. In advanced cases, corneal transplant is the primary treatment option. Effective nonsurgical treatment options would decrease vision loss and the need for corneal transplant. Here we evaluate and compare novel antiangiogenic peptides derived from collagen type IV and type 1 thrombospondin in a murine model of corneal neovascularization.
Corneal neovascularization was induced in thirty, eight-week old C57BL/6 mice using a modified Kenyon et al model. Briefly, b-FGF and sucralfate pellets were implanted into the corneal stroma to induce corneal neovascularization. Peptides derived from collagen type IV (pentastatin-1 and pentastatin-2) and type 1 thrombospondin (wispostatin-1 and thrombostatin-containing-6) were tested for in vivo antiangiogenic activity. Six days after pellet implantation, the number of clock-hours of circumferential corneal neovascularization and vessel length measurements was performed. The area of corneal neovascularization was calculated for each eye by the formula: area (mm2) = 0.2π x CN (mm) x VL (mm).
Thrombostatin-containing-6 and wispostatin-1 provided significant inhibition of corneal neovascularization area in this model, 89% (p=0.0095) and 96% (p=0.0007) respectively, compared to positive control. Pentastatin-1 and 2 decreased corneal neovascularization by 9% and 16% respectively, but these changes were not statistically significant. Negative controls produced no significant area of corneal neovascularization.
Novel peptides derived from thrombospondin type 1 domain-containing proteins such as thrombostatin-containing-6 and wispostatin-1 may represent an effective approach to inhibition of corneal neovascularization. The collagen type IV derived peptides (pentastatin-1 and pentastatin-2) while less promising, showed in vitro inhibition of endothelial cell proliferation and migration. The differential effects observed in vivo may provide mechanistic insights into the pathophysiology of corneal neovascularization.
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