Sustained dasatinib treatment prevents early fibrotic changes following ocular trauma

• Published in: Graefe's archive for clinical and experimental ophthalmology 2021-05, Vol.259 (5), p.1103-1111
• Main Authors: Ueda, Shunichiro, Nunn, Betty M., Chauhan, Rajat, McDonald, Kevin, Kaplan, Henry J., O’Toole, Martin G., Tamiya, Shigeo
• Format: Article
• Language: English
• Subjects: Animals; Basic Science; Biodegradability; Blindness; Chronic myeloid leukemia; Controlled release; Dasatinib - therapeutic use; Enzyme inhibitors; Eye; Eye Injuries - etiology; Eye Injuries - prevention & control; Glycolic acid; Injection; Intravitreal Injections; Medicine; Medicine & Public Health; Myeloid leukemia; Nanoparticles; Ophthalmology; Polylactide-co-glycolide; Protein-tyrosine kinase; Retina; Swine; Trauma; Vitreoretinopathy, Proliferative - drug therapy; Vitreoretinopathy, Proliferative - etiology; Vitreoretinopathy, Proliferative - prevention & control; Young adults
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-020-05037-4

Purpose Posterior ocular trauma and the subsequent fibrotic retinal complication termed proliferative vitreoretinopathy (PVR) are leading causes of blindness in children and young adults. A previous study suggested that changes occurring within the first month post-trauma can lead to development of PVR later. The aim of this study was to examine the effect of dasatinib, a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia, on fibrotic changes occurring within the first month following ocular trauma. Methods A previously established swine ocular trauma model that mimics both contusion and penetrating injuries was used. Dasatinib was administered on days 4 and 18 post-trauma via intravitreal injection of either bolus solution or suspension of a sustained release system incorporated in biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Animals were followed up to day 32, and the development of traction full-thickness fold in the posterior retina was assessed. Results A full-thickness retinal fold extending from the wound site developed in 3 out of 4 control eyes injected with PLGA nanoparticles alone at 1 month. Administration of dasatinib solution had little preventative effect with 6 out of 7 eyes developing a fold. In contrast, dasatinib-incorporated PLGA nanoparticle injection significantly reduced the incidence of fold to 1 out of 10 eyes. Conclusions Injection of dasatinib-incorporated PLGA significantly reduced early fibrotic retinal changes which eventually lead to PVR following posterior ocular trauma. Thus, our sustained dasatinib release system can potentially be used to both prevent and/or broaden the surgical treatment window for PVR.