Abstract
Purpose :
Myo/Nog cells, identified by their expression of MyoD, noggin and the G8 epitope, are present in low numbers throughout the eye, including the lens. Depletion of Myo/Nog cells prevents accumulation of myofibroblasts in explant cultures of human lens tissue. In this study we examined the distribution of Myo/Nog cells following cataract surgery in the rabbit and tested the effects of various doses of the G8 monoclonal antibody (mAb) conjugated to 3DNA nanocarriers intercalated with doxorubicin (G8:3DNA:Dox) and control drugs on the accumulation of myofibroblasts and development of posterior capsule opacification (PCO).
Methods :
Cataract surgery was performed on New Zealand white rabbits. Buffered saline solution (BSS), Dox, G8:3DNA, 3DNA:Dox or G8:3DNA:Dox was injected behind and in front of the intraocular lens. The amount of Dox ranged from 0.7ug/ml to 70ug/ml. Four weeks after surgery, eyes were examined and PCO was scored by slit lamp analysis, gross observation and histologically. Double labeling of tissue sections was performed with antibodies to G8 and noggin or alpha smooth muscle actin (α-SMA) for identification of Myo/Nog cells and myofibroblasts. The authors certify that this research was conducted in compliance with the Statement for the Use of Animals in Ophthalmic and Vision Research.
Results :
Myo/Nog cells are present in the anterior and equatorial zone of the rabbit lens. One month after cataract surgery, α-SMA-positive (+) Myo/Nog cells were present on the posterior lens capsule and overlaid wrinkles in the capsule. Myo/Nog cells also were observed in the ciliary body, external surface of the capsule and on the zonule of Zinn. Few if any G8+ or α-SMA+ cells remained in lenses treated with G8:3DNA:Dox. Both 35 and 70ug/ml G8:3DNA:Dox significantly reduced central and peripheral PCO compared to BSS, G8:3DNA and 3DNA:Dox. Dox alone also reduced PCO when administered at 70ug/ml but was less effective than G8:3DNA:Dox at 35ug/ml. Dox, but not G8:3DNA:Dox, caused corneal edema.
Conclusions :
Myo/Nog cells contribute to PCO, in part, by producing wrinkles in the lens capsule. G8:3DNA:Dox specifically targeted Myo/Nog cells within the lens and decreased PCO in this preclinical trial. Administration of the drug to all patients at the time of surgery may reduce the need for laser treatment to restore visual acuity.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.