ORIGINAL RESEARCH ARTICLE Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes Cibele Rodrigues Toledo . Vinı ´cius Viana Pereira . Lays Fernanda Nunes Dourado . Mayara Rodrigues Branda ˜o Paiva . Armando Silva-Cunha Received: 26 June 2018 / Accepted: 22 February 2019 Ó Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose Investigate the potential application of corosolic acid (CA) in the treatment of diseases causing retinal neovascularization. Methods CA cytotoxicity effect was evaluated in ARPE-19 cells by sulforhodamine B colorimetric method, and antiangiogenic activity was studied using chorioallantoic membrane (CAM) assay. An amount of 0.01 mL of CA formulations at 5, 10 and 25 lM was injected in the right eyes of Wistar rats, and the contralateral eyes received the vehicle to verify the safety of ophthalmic use. Electroretinography (ERG) was performed before, 7 and 15 days after CA administration. Animals were killed on the 15th day, and the histological analysis of retina was carried out under light microscopy. Results CA did not present cytotoxicity at concen- trations below 35.5 lM after 48 h of treatment. The antiangiogenic activity was confirmed by CAM assay, since CA (range from 5 to 25 lM) induced a significant reduction in vascularity without any signs of toxicity. ERG recordings and histological evalua- tion did not show any signs of retinal toxicity. Conclusions CA was effective in reducing vascular- ity in a CAM model and was found to be safe for potential ophthalmic use. Keywords Corosolic acid Á Toxicity Á Antiangiogenic Á Neovascularization process Introduction Vision loss represents an important public health problem all over the world. It is estimated more than 200 million people are moderately or severely visually impaired and 36 million are blind [1, 2]. Proliferative retinal diseases are a common cause of vision loss, like cases of diabetic retinopathy and age-related macular degeneration. Both of these diseases are characterized by abnormal neovascularization. Angiogenesis or neovascularization is a natural process responsible for new blood vessels formation, and it is controlled by proangiogenic and antiangio- genic factors. However, the balance between these factors is lost in some pathological conditions, due to an overexpression of proangiogenic factors. The result is an uncontrolled cell multiplication and formation of neovasculature, which is weak and incompetent, leading to leaks and hemorrhages, which may com- promise the retinal integrity and, progressively, the visual function [3]. Thus, the inhibition of C. R. Toledo (&) Á V. V. Pereira Á L. F. N. Dourado Á M. R. B. Paiva Á A. Silva-Cunha Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil e-mail: ci.toledo02@gmail.com 123 Doc Ophthalmol https://doi.org/10.1007/s10633-019-09682-x