Ocular safety of intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization

Ramin Nourinia, Mozhgan Rezaei Kanavi, Amir Kaharkaboudi, Seyed Iman Taghavi, Seyed Javid Aldavood, Soesiawati R. Darjatmoko, Shoujian Wang, Zafer Gurel, Jeremy A. Lavine, Sare Safi, Hamid Ahmadieh, Narsis Daftarian, Nader Sheibani*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

PURPOSE. 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 lg in 2 lL) 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.

Original languageEnglish (US)
Pages (from-to)8228-8235
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number13
DOIs
StatePublished - Dec 1 2015

Keywords

  • Choroidal neovascularization
  • Electroretino- graphy
  • Glial fibrillary acidic protein
  • Intravitreal injections
  • Propranolol

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Nourinia, R., Kanavi, M. R., Kaharkaboudi, A., Taghavi, S. I., Aldavood, S. J., Darjatmoko, S. R., Wang, S., Gurel, Z., Lavine, J. A., Safi, S., Ahmadieh, H., Daftarian, N., & Sheibani, N. (2015). Ocular safety of intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization. Investigative Ophthalmology and Visual Science, 56(13), 8228-8235. https://doi.org/10.1167/iovs.15-17169