title: Ocular Safety of Intravitreal Propranolol and Its Efficacy in Attenuation of Choroidal Neovascularization.
abstract: OBJECTIVE
  Determine the safe dose of intravitreal propranolol (IVP), and evaluate its inhibitory effect on laser-induced choroidal neovascularization (CNV).
  
  
  METHODS
  To determine the IVP safe dose, 32 rabbits were divided into 4 groups. Three of these groups received IVP (15 μL) corresponding to 15 μg (group B), 30 μg (group C), and 60 μg (group D). The control group (A) received 15 μL saline. Safety was assessed by ocular examination, electroretinography (ERG), routine histopathologic evaluation, immunohistochemistry for glial fibrillary acidic protein (GFAP), and real-time qPCR for GFAP, VEGF, thrombospondin 1 (TSP1), and pigment epithelium-derived factor (PEDF). A similar experiment was performed in 24 mice by using a 100-fold lower amount of propranolol (0.15, 0.3, and 0.6 μg in 2 μL) based on vitreous volume. For assessment of the angioinhibitory effects of IVP, CNV was induced in 42 mice via laser burns. Mice were divided into two groups: group 1 received the safe dose of IVP (0.3 μg in 2 μL) and group 2 received saline. Neovascularization area was quantified by intercellular adhesion molecule (ICAM)-2 immunostaining of choroidal-scleral flat mounts by using ImageJ software.
  
  
  RESULTS
  According to clinical, ERG, and histopathologic findings, 30 μg IVP was chosen as the safe dose in rabbit eyes, comparable to 0.3 μg IVP in mouse eyes. As compared to the control eyes, the development of CNV was attenuated (4.8-fold) in mice receiving 0.3 μg IVP.
  
  
  CONCLUSIONS
  Intravitreal propranolol injection up to the final dose of 30 μg in rabbits and 0.3 μg in mice was safe, and was effective in attenuation of CNV in mice.
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Nourinia
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Rezaei Kanavi
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Kaharkaboudi
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Seyed Iman
authors.initials: SI
authors.lastname: Taghavi
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Seyed Javid
authors.initials: SJ
authors.lastname: Aldavood
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Soesiawati R
authors.initials: SR
authors.lastname: Darjatmoko
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Shoujian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Zafer
authors.initials: Z
authors.lastname: Gurel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Lavine
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sare
authors.initials: S
authors.lastname: Safi
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Narsis
authors.initials: N
authors.lastname: Daftarian
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States 5McPherson Eye Research Institute, University Wisconsin School of Medicine and Public Health, Madison, Wiscons.
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D002829:Choroid / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D058449:Intravitreal Injections; D051379:Mice; D011433:Propranolol / Q000008:administration & dosage*; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol