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

doi:10.1167/iovs.15-17169

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

Ophthalmology

Research output: Contribution to journal › Article › peer-review

24 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 language	English (US)
Pages (from-to)	8228-8235
Number of pages	8
Journal	Investigative Ophthalmology and Visual Science
Volume	56
Issue number	13
DOIs	https://doi.org/10.1167/iovs.15-17169
State	Published - Dec 1 2015

Funding

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.

Keywords

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

ASJC Scopus subject areas

Sensory Systems
Cellular and Molecular Neuroscience
Ophthalmology

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10.1167/iovs.15-17169

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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

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title = "Ocular safety of intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization",

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.",

keywords = "Choroidal neovascularization, Electroretino- graphy, Glial fibrillary acidic protein, Intravitreal injections, Propranolol",

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

note = "Publisher Copyright: {\textcopyright} 2015 The Association for Research in Vision and Ophthalmology, Inc.",

year = "2015",

month = dec,

day = "1",

doi = "10.1167/iovs.15-17169",

language = "English (US)",

volume = "56",

pages = "8228--8235",

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number = "13",

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Nourinia, R, Kanavi, MR, Kaharkaboudi, A, Taghavi, SI, Aldavood, SJ, Darjatmoko, SR, Wang, S, Gurel, Z, Lavine, JA, 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, vol. 56, no. 13, pp. 8228-8235. https://doi.org/10.1167/iovs.15-17169

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

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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ER -

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

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