Inhibitory Effect of Oral Doxycycline on Neovascularization in a Rat Corneal Alkali Burn Model of Angiogenesis

Abstract

Purpose: To examine the efficacy of oral doxycycline treatment (as compared to oral and topical dexamethasone) for inhibiting corneal neovascularization (CNV). Methods: Following corneal alkali burn, rats were treated daily with oral doxycycline, oral dexamethasone, or topical dexamethasone for 14 days. Control rats were injured but were not treated. At days 3, 7, and 14 post injury, length and area of CNV were evaluated, as well as corneal epithelial healing and ulceration. Tissues were obtained from a subset of rats from each group for histopathological analysis. Results: At days 7 and 14 post-injury, CNV length in the doxycycline group was significantly less than in the untreated control (p < 0.008). The area of CNV was significantly smaller in doxycycline as compared to control rats on days 3, 7, and 14 post-injury. Inhibition of CNV (indicated by area and length) was significantly greater in both dexamethasone groups compared to the doxycycline group (p < 0.008 for all comparisons). However, epithelial healing was significantly more rapid in the doxycycline group compared to both dexamethasone groups (p < 0.008). Epithelial ulceration was apparent in both oral and topically treated dexamethasone rats, but not in doxycycline-treated rats. Conclusions: Oral doxycycline inhibits CNV without the harmful side effects associated with dexamethasone use. Further investigation is warranted to assess the mechanisms through which doxycycline acts to cause CNV inhibition, and the applicability of doxycycline use for treating CNV in the clinical setting.