The Effect of Combinations of Flurbiprofen, Low Molecular Weight Heparin, and Doxycycline on the Inhibition of Corneal Neovascularization
University of Illinois at Chicago, Chicago, Illinois, United States Cornea
(Impact Factor: 2.04).
07/2006; 25(5):582-5. DOI: 10.1097/01.ico.0000220767.73660.3a
To determine the efficacy of various combinations of flurbiprofen, low molecular weight heparin (LMWH), and doxycycline on the inhibition of corneal neovascularization in rats.
Chemical cauterization of the cornea in 32 eyes of 32 rats was performed using silver nitrate/potassium nitrate sticks. The animals were divided into 4 groups. Topical instillation of 0.015% flurbiprofen with 5 mg/mL LMWH (group 1); flurbiprofen with 10 mg/mL doxycycline (group 2); doxycycline with LMWH (group 3), and saline (group 4; control) was performed twice a day for 7 days. Slit-lamp photography was used to determine the percent areas of cornea covered by neovascularization and also by scar in each group. The means were compared to find any significant (P < 0.05) difference between groups. The animals were euthanized and the eyes enucleated for histological evaluation.
The mean of percent area of corneal neovascularization 5 in group 1 was 48.5 +/- 13.1; group 2, 6.6 +/- 5.5; group 3, 22.0 +/- 27.6 and group 4, 64.6 +/- 9. The means of percent area of neovascularization in groups 2 and 3 were significantly lower compared with control and group 1. There was no significant difference in the percent corneal neovascularization between groups 2 and 3 or between group 1 and the control group. Histological findings were consistent with slit-lamp evaluations.
Topical instillation of combinations of doxycycline with either flurbiprofen or LMWH can effectively inhibit corneal neovascularization made by chemical cauterization of the cornea in rats.
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- "Therapies inhibiting MMP-9 are thus believed to have potential for inhibiting neovascularization. Previously, it has been shown that tetracycline and its derivatives inhibit corneal neovascularization via suppressing MMP-9 activity, a role that is distinct from its antimicrobial activity    . Tigecycline is a newer and more powerful agent of the tetracycline family, which is available as an injectable antibiotic . "
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ABSTRACT: Objective. To investigate the effects of topical and subconjunctival tigecycline on the prevention of corneal neovascularization. Materials and Methods. Following chemical burn, thirty-two rats were treated daily with topical instillation of 1 mg/mL tigecycline (group 1) or subconjunctival instillation of 1 mg/mL tigecycline (group 3) for 7 days. Control rats received topical (group 2) or subconjunctival (group 4) 0.9% saline. Digital photographs of the cornea were taken on the eighth day after treatment and analyzed to determine the percentage area of the cornea covered by neovascularization. Corneal sections were analyzed histopathologically. Results. The median percentages of corneal neovascularization in groups 1 and 3 were 48% (95% confidence interval (CI), 44.2–55.8%) and 33.5% (95% CI, 26.6–39.2%), respectively. The median percentages of corneal neovascularization of groups 1 and 3 were significantly lower than that of the control group (
, resp.). Histologic examination of samples from groups 1 and 3 showed lower vascularity than that of control groups. Conclusion. Topical and subconjunctival administration of tigecycline seems to be showing promising therapeutic effects on the prevention of corneal neovascularization. Furthermore, subconjunctival administration of tigecycline is more potent than topical administration in the inhibition of corneal neovascularization.
- "Minocycline and doxycycline are two widely used second-generation, semi-synthetic tetracycline analog. Doxycycline has shown a capacity for inhibiting CNV in rats by topical and systemic use , , . Minocycline has seldom been used in CNV models. "
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ABSTRACT: The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV). A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS) or minocycline twice a day (60 mg/kg or 30 mg/kg) for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs). The mRNA expression levels of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMPs), interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6) were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d.) can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.
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- "Various compounds have been identified as inhibitors in experimental and clinical corneal NV. These include steroids , non-steroidal anti-inflammatory drugs, heparin, doxycycline and cyclosporine A, methotrexate and thalidomide (Benelli et al. 1997; Kruse et al. 1998; Joussen et al. 1999; Peyman et al. 2006; Riazi-Esfahani et al. 2006). Topical steroids are still the mainstay of the prevention and treatment of corneal NV, but they may be associated with serious complications such as cataract, glaucoma and infections (Fraunfelder & Rich 2003). "
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ABSTRACT: This study aimed to evaluate the effects of different concentrations of topically administered bevacizumab (Avastin) on experimental corneal neovascularization (NV) in rats.
Corneal NV was induced by chemical cauterization with silver nitrate sticks applied to the centre of the corneas of 37 Wistar rats. The rats were then randomized to four topical treatment groups: group 1 (n = 10) received 4 mg/ml bevacizumab; group 2 (n = 9) received 2 mg/ml bevacizumab; group 3 (n = 10) received 1 mg/ml bevacizumab, and group 4 (n=8) represented a control group and received saline. All drops were initiated immediately after cauterization and applied twice per day for 7 days. Corneal NV was assessed 8 days after cauterization in a masked fashion, both qualitatively by clinical evaluation and quantitatively by blood vessel count in photographs of histological sections.
On clinical evaluation, groups 1 and 2 showed significantly less NV compared with the saline-treated control group (p = 0.006 and p = 0.024, respectively). Histopathological evaluation showed that only group 1 differed significantly from controls (5% significance level) and normal corneal epithelium was seen in all groups.
Topically administered bevacizumab at a concentration of 4 mg/ml significantly reduces corneal NV according to both clinical and histopathological evaluations; lower concentrations were less effective on both parameters. No corneal epitheliopathy was found using these concentrations.
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