Abstract
Purpose:
Posterior Capsule Opacification (PCO) is a vision impairing disease that occurs in some adults and most children following cataract surgery. In fibrotic PCO, myofibroblasts migrate onto the posterior capsule and contract to produce wrinkles that affect visual acuity. Myofibroblasts are derived from Myo/Nog cells that express the skeletal muscle transcription factor MyoD, the BMP inhibitor Noggin and the G8 protein. Ex vivo depletion of Myo/Nog cells in human lens tissue had been achieved by incubating explants with the G8 monoclonal antibody (mAb) and complement. The goal of this study was to test the specificity and efficacy of the G8 mAb complexed to 3DNA nanocarriers intercalated with Doxorubicin (G8-3DNA-Dox) in explants of human lens tissue and rabbits undergoing cataract surgery.
Methods:
Anterior human lens tissue obtained by capsulorhexis was cultured in serum free medium. Lens explants were incubated with G8-3DNA-Dox, G8-3DNA or 3DNA-Dox. Explants were assayed for apoptosis using TUNEL. Rabbits were injected with either balanced salt solution (BSS) or G8-3DNA-Dox at doses of 7.0 or 70ug/ml. The rabbits were observed for a period of four weeks for the development of adverse reactions, including PCO.
Results:
G8-3DNA-Dox specifically targeted and induced apoptosis in Myo/Nog cells in human lens tissue. Control conjugates did not affect Myo/Nog or lens epithelial cells. G8-3DNA-Dox also targeted Myo/Nog cells in the lens of rabbits that underwent cataract surgery. Slit lamp, gross exam and histopathology analyses revealed that rabbits injected with 70ug/ml of G8-3DNA-Dox had mostly clear posterior capsules with scant areas of PCO without fibrosis. Control rabbits injected with BSS or 7.0 ug/ml G8-3DNA-Dox developed extensive PCO and fibrosis
Conclusions:
Antibody-3DNA nanocarriers are highly specific reagents for delivering cytotoxic cargo to a subpopulation of cells. The 3DNA nanocarriers themselves are nontoxic. Administration of G8-3DNA-Dox at the time of cataract surgery may reduce the incidence of PCO and maintain vision.