Ocular Safety of Intravitreal Propranolol and Its Efficacy in Attenuation of Choroidal Neovascularization

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 mu L) corresponding to 15 mu g (group B), 30 mg (group C), and 60 mg (group D). The control group (A) received 15 mu L 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 mg in 2 mu L) 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 mg in 2 mu L) 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 mg IVP was chosen as the safe dose in rabbit eyes, comparable to 0.3 mg IVP in mouse eyes. As compared to the control eyes, the development of CNV was attenuated (4.8-fold) in mice receiving 0.3 mg IVP. CONCLUSIONS. Intravitreal propranolol injection up to the final dose of 30 mg in rabbits and 0.3 mg in mice was safe, and was effective in attenuation of CNV in mice.