TY - JOUR
T1 - Ocular safety of intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization
AU - Nourinia, Ramin
AU - Kanavi, Mozhgan Rezaei
AU - Kaharkaboudi, Amir
AU - Taghavi, Seyed Iman
AU - Aldavood, Seyed Javid
AU - Darjatmoko, Soesiawati R.
AU - Wang, Shoujian
AU - Gurel, Zafer
AU - Lavine, Jeremy A.
AU - Safi, Sare
AU - Ahmadieh, Hamid
AU - Daftarian, Narsis
AU - Sheibani, Nader
N1 - Funding Information:
Supported by R24 EY022883 and P30 EY016665 from the National Institutes of Health, and an unrestricted departmental award from Research to Prevent Blindness (to NS). NS is a recipient of Alice R. McPherson-Retina Research Foundation Chair.
Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Choroidal neovascularization
KW - Electroretino- graphy
KW - Glial fibrillary acidic protein
KW - Intravitreal injections
KW - Propranolol
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U2 - 10.1167/iovs.15-17169
DO - 10.1167/iovs.15-17169
M3 - Article
C2 - 26720475
AN - SCOPUS:84952936746
SN - 0146-0404
VL - 56
SP - 8228
EP - 8235
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 13
ER -