Versity of Health-related Sciences, No. 23, Paidarfard St. Boostan 9 St. Pasdaran Avenue
Versity of Medical Sciences, No. 23, Paidarfard St. Boostan 9 St. Pasdaran Avenue, Cathepsin B Protein Formulation Tehran 16666, Iran; [email protected]. Submitted: April 24, 2015 Accepted: November 20, 2015 Citation: Nourinia R, Rezaei Kanavi M, Kaharkaboudi A, et al. Ocular security of GM-CSF Protein Biological Activity intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2015;56:8228235. DOI:10.1167/iovs.15-PURPOSE. Figure out the safe dose of intravitreal propranolol (IVP), and evaluate its inhibitory impact on laser-induced choroidal neovascularization (CNV). Techniques. To ascertain the IVP secure dose, 32 rabbits had been divided into four groups. 3 of those groups received IVP (15 lL) corresponding to 15 lg (group B), 30 lg (group C), and 60 lg (group D). The control group (A) received 15 lL 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 element (PEDF). A equivalent experiment was performed in 24 mice by utilizing a 100-fold reduce amount of propranolol (0.15, 0.three, and 0.six lg in 2 lL) depending on vitreous volume. For assessment of your angioinhibitory effects of IVP, CNV was induced in 42 mice via laser burns. Mice have been divided into two groups: group 1 received the secure dose of IVP (0.3 lg in 2 lL) and group 2 received saline. Neovascularization region was quantified by intercellular adhesion molecule (ICAM)-2 immunostaining of choroidal cleral flat mounts by using ImageJ software program. Outcomes. In line with clinical, ERG, and histopathologic findings, 30 lg IVP was chosen as the secure dose in rabbit eyes, comparable to 0.3 lg IVP in mouse eyes. As in comparison to the control eyes, the improvement of CNV was attenuated (4.8-fold) in mice getting 0.three lg IVP. CONCLUSIONS. Intravitreal propranolol injection up to the final dose of 30 lg in rabbits and 0.3 lg in mice was secure, and was successful in attenuation of CNV in mice. Key phrases: choroidal neovascularization, intravitreal injections, propranolol, electroretinography, glial fibrillary acidic proteinhoroidal neovascularization (CNV) can be a big cause of visual loss specifically in the elderly. Recent studies1,two have established a essential role for improved production of vascular endothelial growth element (VEGF) in the development and progression of CNV. Vascular endothelial development aspect is secreted from the basal side from the retinal pigment epithelium (RPE) toward the choroid, and higher levels of VEGF receptors, for example kinase insert domain receptor (KDR/VEGFR2) and fmsrelated tyrosine kinase-4 (FLT-4/VEGFR3), are located around the choriocapillaris endothelium facing the RPE layer.three,four While overexpression of VEGF in RPE cells is sufficient to induce CNV in rats, the function of other regulatory aspects inside the pathogenesis of human CNV can not be excluded.1,5 Propranolol can be a nonselective b-adrenergic receptor (b-AR) blocking agent that specifically competes with b-AR agonists for instance epinephrine and norepinephrine at the b1- or b2-AR web-sites.eight An in vitro study9 has shown that propranolol inhibits angiogenesis via attenuation of proliferation, migration, and differentiation of endothelial cells. Moreover, this study reports that propranolol inhibits VEGF overexpression andCdecreases induction of tyrosine phosphorylation of VEGFR-2; this inhibits activation of the extracellular signal egulated kinase-1/2 an.