Abstract
Purpose:
To evaluate the therapeutic effects of early and late subconjunctival injection of bevacizumab on the inhibition of corneal neovascularization (NV) in a rabbit closed eye contact lens (CL) wear model. The underlyng mechanism focusing on VEGF and VEGF receptors were also evaluated.
Methods:
Corneal NV was induced by closed eye CL wear in rabbits. Group 0 included rabbits eyes without bevacizumab treatment. Weekly subconjunctival injections of bevacizumab (5.0 mg) for 1 month were started immediately (Group I) and 1 month after induction of corneal NV with continuous induction (Group II. Digital photographs were taken weekly. The percentage of involved corneal surface (PICS)/centricity/extent of corneal NV were evaluated. Immunohistochemical staining was used to determine the intracorneal diffusion of bevacizumab in the different groups. Immunostaining with anti-CD31, α- smooth muscle actin (αSMA) and high-molecular-weight melanoma-associated antigen (HMW-MAA) was used to evaluate the formation of pericytes and smooth muscle around the corneal NV. The expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1, VEGFR2) was also evaluated. TUNEL staining was performed to evaluate cellular apoptosis after bevacizumab injection. In each group, 6 rabbtit eyes were examined. There were 6 eyes in each experimental conditions
Results:
Early treatment with bevacizumab (Group I) more significantly inhibited corneal NV than late treatment administered (Group II) after 4 weeks (p<0.01 in NV length, surface area and extent). Immunostaining showed pericyte and smooth muscle coverage on the vessel wall as early as 2 weeks after induction. Intracorneal diffusion of bevacizumab was not different among the 3 groups. VEGF/VEGFR1/VEGFR2 expressed on corneal epithelial cells was found in group 0/1/2, and on corneal vessels in group 0/2 but not group 1. Corneal vessels with evidence of apoptosis was not found in group 1 and group 2 at 4 weeks after bevacizmbab injection.
Conclusions:
Early but not late injection of bevacizumab inhibited corneal NV induced by closed eye CL wear in rabbits. The difference in therapeutic effect was not related to intracorneal diffusion of bevacizumab. Bevacizumab did not influence the expression of VEGF/VEGFR1/VEGFR2 on corneal vessels if treated late.
Keywords: 609 neovascularization •
748 vascular endothelial growth factor •
480 cornea: basic science