Posterior capsule opacification (PCO) occurs in some adults and most children following cataract surgery. The fibrotic form of PCO arises, in part, from migratory, contractile myofibroblasts that deform the lens capsule and impair vision. In short-term cultures of human anterior lens tissue, myofibroblasts emerge from Myo/Nog cells that are identified with the G8 monoclonal antibody and by their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study, we tested the hypothesis that targeted depletion of Myo/Nog cells with the G8 monoclonal antibody (mAb) conjugated to three-dimensional DNA nanocarriers intercalated with doxorubicin (G8:3DNA:Dox) would prevent the accumulation of myofibroblasts in long-term, serum- and growth factor-free cultures of human lens tissue obtained by capsulorhexis. The mAb:nanocarrier complex was internalized into acidic compartments of the cell. G8:3DNA:Dox killed nearly all Myo/Nog cells without affecting the lens epithelial cells. In 30-day cultures, all G8-positive cells expressed noggin, and subpopulations had synthesized MyoD, sarcomeric myosin, and alpha smooth muscle actin (α-SMA). Myo/Nog cells responded to scratching of the lens epithelium by accumulating around the edges of the wound. Treatment with two doses of G8:3DNA:Dox completely eliminated G8+/α-SMA+ cells throughout the explant. These experiments demonstrate that Myo/Nog cells are the source of myofibroblasts in long-term cultures of anterior human lens tissue and mAb:3DNA nanocarriers specifically and effectively deliver cytotoxic cargo to a subpopulation of cells without off-target effects. G8:3DNA:Dox has the potential to reduce PCO following cataract surgery.
- Received November 18, 2016.
- Accepted January 3, 2017.
↵1 Current affiliation: Philadelphia College of Osteopathic Medicine, Philadelphia, PA.
↵2 Co-senior authors.
This study was supported by the Sharpe-Strumia Research Foundation.
An abstract of this work was presented at the 2016 ARVO Annual Meeting, Seattle, WA, May 1–5, and published as: Gerhart JV, Greenbaum M, Getts R, and George-Weinstein M (2016) Long term culture of human lens tissue for screening drugs with the potential to prevent PCO. Invest Ophthalmol Vis Sci 57 (abstract issue):3996, Association for Research in Vision and Ophthalmology, Rockville, MD.
- Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics