title: Effects of a human VEGF antibody (Bevacizumab) on deprivation myopia and choroidal thickness in the chicken.
abstract: Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein which is responsible for neovascularization and fenestrations of the choriocapillaris. In neovascular maculopathies secondary to age-related degeneration (nAMD) or pathologic myopia (PM-CNV), its inhibition by humanized antibodies is currently the most successful therapy. The choroid has an important role in maintaining retinal health and its thickness declines with age and with myopia. Since choroidal thickness depends on its perfusion rate, one would expect that anti-VEGF agents can also change choroidal thickness. We have tested the hypothesis in the chicken model, using a humanized antibody, Bevacizumab, and also studied the distribution of VEGF-A in the chicken fundal layers by immunohistochemical techniques. Even though it was raised against human VEGF, Bevacizumab had several long lasting effects in the chicken eye (1) after a single unilateral intravitreal injection of 0.5 mg, it partially suppressed the development of deprivation myopia, similarly in both eyes, (2) it completely suppressed choroidal thickening that normally occurs when eyes recover from induced myopia over a time period of about 10 days, (3) it had little effect on the choroidal thickness in eyes that had normal visual experience, (4) VEGF-A was absent in sclera, but highly expressed in the walls of choroidal blood vessels and presumed nerve fiber bundles, as well as in retinal photoreceptors and cells of the inner and outer nuclear layer. One day after the injection of Bevacizumab, the immunoreactivity against VEGF-A had largely disappeared. In conclusion, Bevacizumab is similary effective in human and chicken tissue, has similar time constants (few days), has almost symmetrical effects on myopia in both eyes even after monocular application, and fully suppresses choroidal thickening that normally occurs during recovery from deprivation myopia. The mechanisms by which Bevacizumab acts on the choroidal thickness are perhaps most interesting, both to better understand the role of the choroid in myopia development but also to clarify its potential side effects during nAMD and PM-CNV treatment in the clinics.
authors.affiliation: Section of Neurobiology of the Eye, Ophthalmic Research Institute, University of Tuebingen, Calwerstrasse 7/1, 72076 Tübingen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Mathis
authors.affiliation: University Eye Hospital, Department of Ophthalmology, Schleichstrasse 12-16, 72076 Tuebingen, Germany.
authors.forename: Focke
authors.initials: F
authors.lastname: Ziemssen
authors.affiliation: Section of Neurobiology of the Eye, Ophthalmic Research Institute, University of Tuebingen, Calwerstrasse 7/1, 72076 Tübingen, Germany. Electronic address: frank.schaeffel@uni-tuebingen.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Schaeffel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D058452:Axial Length, Eye / Q000473:pathology; D000068258:Bevacizumab; D002645:Chickens; D002829:Choroid / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D008297:Male; D009216:Myopia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D012683:Sensory Deprivation; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: VEGF; bevacizumab; chicken; choroid; myopia