Development of a new animal model of radiation retinopathy using an experimental radiation platform

Abstract

AbstractPurposeChoroidal melanoma is the most frequent malignant intraocular tumor. Radiotherapy using various modalities is the standard conservative treatment for confined lesions. It allows globe preservation in most cases, but 50% to 60% of irradiated eyes develop radiation retinopathy, secondary to multiple retinal vascular occlusions, leading in the most severe cases to neovascular glaucoma and secondary enucleation. The purpose of this experimental study was to create and test a new model of radiation retinopathy in the rat retina, and to explore potential pathways involved in the early pathogenesis of radiation retinopathy.MethodsWe used the Small Animal Radiation Research Platform (SARRP, Xstrahl, UK) to build a dose‐response model of retinal irradiation. Long‐Evans rats were irradiated with an X‐ray source, after exorbiting the eye. Only one eye was irradiated for ethical reasons. There were 4 groups of 4 animals according to the radiation dose received. Group 1 received one 15‐Gray fraction of, Group 2 received two 15‐Gray fractions, Group 3 received three 15‐Gray fractions, and Group 4, the control group, received one sham irradiation fraction.Multimodal imaging with OCT, color fundus photograph, and fluoresceine angiography (Micron 4, Phoenix Researchlabs, USA) was performed at baseline and seven days after irradiation.Animals were sacrificed 8 days after irradiation. Eyes were either fixated for inclusion and sections, fixated for flat‐mounts of retina/RPE, or milled for Western Blot analysis.ResultsIrradiating of rat retinas using SARRP was successful. At day 7, there were no specific features on angiography, but OCT revealed inconsistent features in the peripheral retina of one animal (Group 3 fractions). In two animals, exorbitation was not possible due to variations of periocular morphology (Groups 2 and 3 fractions). Both animals developed corneal opacifications attributed to lacrymal gland damage.ConclusionsSARRP is a simple and efficient tool to model radiation retinopathy in small animals. Further work is required to improve our understanding of this potentially blinding complication of ocular irradiationReferencesRamos MS, Echegaray JJ, Kuhn‐Asif S, Wilkinson A, Yuan A, Singh AD, Browne AW.Animal models of radiation retinopathy ‐ From teletherapy to brachytherapy.Exp Eye Res. 2019 Apr;181:240‐251. Rothschild PR, Salah S, Berdugo M, Gélizé E, Delaunay K, Naud MC, Klein C, Moulin A, Savoldelli M, Bergin C, Jeanny JC, Jonet L, Arsenijevic Y, Behar‐Cohen F, Crisanti P. ROCK‐1 mediates diabetes‐induced retinal pigment epithelial and endothelial cell blebbing: Contribution to diabetic retinopathy. Sci Rep. 2017 Aug 18;7(1):8834.Rousseau M, Gaugler M‐H, Rodallec A, Bonnaud S, Paris F, Corre I. RhoA GTPase regulates radiation‐induced alterations in endothelial cell adhesion and migration. Biochem Biophys Res Commun. 2011;414(4):750‐755.