ABSTRACT
PURPOSE: Bevacizumab is a potent recombinant humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). The purpose of this study was to evaluate the therapeutic effect of subconjunctival injection of bevacizumab on corneal neovascularization (NV) in different rabbit models. METHODS: Several rabbit models of corneal NV were used, including (1) a corneal micropocket assay with VEGF pellet, (2) a corneal micropocket assay with basic fibroblast growth factor (b-FGF) pellets, (3) mechanical limbal injury-induced corneal NV, and (4) an alkali-induced model of corneal NV. Subconjunctival injections of bevacizumab (0.25-2.5 mg) were applied twice per week for 2 to 8 weeks. Digital photographs of the cornea were analyzed to determine the length of corneal NV and the area of cornea covered by NV as a percentage of the total corneal area. Immunohistochemical staining with anti-human IgG antibody labeled with Cy3 was used to determine the detection of intracorneal distribution of bevacizumab after injection. RESULTS: Subconjunctival injection of bevacizumab caused significant inhibition of corneal NV formation as measured by length or surface area in all animal models (P<0.05). No significant ocular complications were found. Staining of bevacizumab was found in the corneal stroma for 3 to at least 14 days in the different rabbit models. CONCLUSIONS: Subconjunctival injection of bevacizumab is effective in inhibiting corneal NV in several rabbit models. Bevacizumab may diffuse into the corneal stroma and persist for a few days after injection. It may be useful in preventing corneal NV in the acute phase of various kinds of corneal inflammation.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/therapeutic use , Corneal Neovascularization/drug therapy , Disease Models, Animal , Angiogenesis Inhibitors/administration & dosage , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Bevacizumab , Blotting, Western , Carbocyanines/metabolism , Conjunctiva , Corneal Neovascularization/metabolism , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Female , Fluorescent Antibody Technique, Indirect , Fluorescent Dyes/metabolism , Injections , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Rabbits , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Maxillary bone epithelial cyst is rare in dogs. A 5-year-old, spayed female miniature schnauzer developed a swelling below the nasal canthus of left eye. Plain radiograph demonstrated a 1.5 cm diameter of radiolucent lesion on the maxillary bone anteroventral to the eye, and contrast dacryocystorhinography confirmed an obstructed nasolarcrimal duct. The swelling showed poor response to antibiotic treatment but responded well to oral prednisolone. Exploratory surgery revealed a cyst-like structure filled with brown serous fluid. Histopathological examination of the removed cyst revealed a double cuboidal epithelial cyst. The dog recovered rapidly after surgery, and the swelling had not recurred for a 36-month follow-up. It is the first case of periorbital bone epithelial cyst reported in an adult miniature schnauzer.
Subject(s)
Bone Cysts/veterinary , Dog Diseases/pathology , Dog Diseases/surgery , Maxilla/diagnostic imaging , Animals , Bone Cysts/drug therapy , Bone Cysts/pathology , Bone Cysts/surgery , Dog Diseases/drug therapy , Dogs , Female , Prednisolone/therapeutic use , RadiographyABSTRACT
Retinal ischemia is a common cause of visual impairment for humans and animals. Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic injury were investigated using a rat model. Retinal ganglion cells (RGCs) were retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the superior collicoli of test Sprague-Dawley rats. High intraocular pressure and retinal ischemia were induced seven days subsequent to such FG labeling. A dose of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at two time points, namely 30 min prior to the induction of retinal ischemia and 1 h subsequent to the cessation of the procedure inducing retinal ischemia. The test-rat retinas were collected seven days subsequent to the induction of retinal ischemia, and densities of surviving RGCs were estimated by counting FG-labeled RGCs within the retina. Histological analysis revealed that ischemic injury caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA-treated groups, almost 100% of the RGCs were preserved by a pre-ischemia treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly reduced the level of ischemia-associated loss of thickness of the total retina, especially the inner retina, and the inner plexiform layer of retina. Besides, PBA treatment significantly reduced the ischemia-induced loss of cells in the ganglion-cell layer of the retina. Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction.
