Evaluation of Intravitreal Toxicity of Somatostatin Conjugate (JF-10-81), an Antiangiogenic Compound

Abstract

Abstract: : Purpose: To evaluate the ocular toxicity of intravitreous somatostatin conjugate, a new angiogenesis inhibitor. Methods: Twenty-four New Zealand albino rabbits were divided into 6 groups (n=4). The animals were anesthetized and treated according to the ARVO resolution. Three animals in each group (one eye per animal) were injected intravitreally with somatostatin in a concentration of 10^-8 M, 10 ^-7 M, 10 ^-6 M, 10 ^-5 M, 10 ^–4 M, or 10 ^-3 M. The fourth animal in each group served as a control and was injected intravitreally with 0.17 ml of sterile water. The injections were made through the pars plana using a 25-gauge needle positioned behind the lens. An anterior chamber paracentesis was performed to reduce the intraocular pressure. All animals were examined before and after injection using the indirect ophthalmoscope and slit-lamp biomicroscopy. Baseline and postinjection electroretinography was performed. The animals were followed up to 14 days postinjection before being sacrificed; the eyes were enucleated and prepared for histologic examination using 2% paraformaldehyde, 3% glutaraldehyde fixative. After fixation for 48 hours, the globes were cut and placed in phosphate buffer solution (PBS). Various concentrations of ethanol were used for dehydration. For pre-infiltration, ethanol and Technovit 7100 were used and the eyes were infiltrated overnight using Technovit 7100. The tissues were embedded in methacrylate overnight and were cut at 3 µm, then stained with 1% Toluidine blue. Results: No clinical changes was seen in Groups 1 to 4 (10^–5 M, 10 ^-6 M, 10 ^-7 M, 10^-8 M, respectively). Electroretinography, which showed decreasing b-wave amplitude in Groups 5 and 6 (10^-4 M and 10^-3M, respectively ), was normal in all other groups. Cataracts and vitreous reaction developed in Groups 5 and 6. Histological examination was normal in all groups. The reduced amplitude in the electroretinogram was explained on the basis of cataract formation in these eyes. Conclusions: Somatostatin conjugate injected intravitreally appeared safe at dosages of 10^-5 M or less. All ocular structures were normal at concentrations of 10^-5 M or below.

Keywords: neovascularization • retinal neovascularization • choroid: neovascularization