Posterior capsule opacification (PCO), caused by the proliferation and migration of residual lens epithelial dells (LECs), is the most frequent complication of extracapsular cataract extraction and IOL implantation. PCO, in conjunction with the accompanying fibrosis and capsular wrinkling and tensing, not only affects postoperative vision, but also induces anterior to posterior capsular adhesions to each other and to the IOL haptics. The latter may substantially limit the movement of the capsule, and interfere with the function of putatively accommodating lOLs. Investigators have been searching for mechanical and pharmaceutical methods to remove or destroy residual LECs. However, none of them has been proven sufficiently practical, effective and/or safe for routine clinical practice. Novel methods/agents to prevent PCO are still needed. Since the actin cytoskeleton plays a crucial role in cell division, migration and adhesion, disruption of the actin cytoskeleton and inhibition of actomyosin contractility by cytoskeletal drugs may prevent PCO and accompanying changes by facilitating clearance of residual LECs from the capsular bag during surgery, inhibiting proliferation and migration of residual LECs after surgery, and/or reducing lens capsular wrinkling and tensing after surgery. The cytoskeletal drugs used in this project have few toxic effects on the cornea and other ocular tissues, which is important for safety consideration. To test the hypotheses described above, extracapsular lens extraction will be conducted in live rabbit eyes and donated human eyes. The number/area of residual LECs immediately after surgery will be evaluated by light microscopy (LM) in lens capsules obtained from the eye receiving a single treatment with the drug(s) or vehicle during surgery. Effects of cytoskeletal drugs on proliferation and migration of LECs and capsular wrinkling and tensing after surgery will be determined in live rabbit eyes receiving chronic drug/vehicle treatments or in cultured human lens capsular bag receiving long-term incubation with the drug/vehicle solution. PCO and accompanying changes in the two models will be observed by slit lamp or microscope for 4 or more weeks, recorded by photography and/or videography for further quantitation, and eventually evaluated by LM. The effect of long- term treatment with the drug(s) on PCO formation will provide evidence for future studies with sustained release of the drug in the capsular bag or drug-coated lOLs in living animals or humans. ? ? ? ?
| Sureshkumar, Jeyalakshmi; Haripriya, Aravind; Muthukkaruppan, Veerappan et al. (2012) Cytoskeletal drugs prevent posterior capsular opacification in human lens capsule in vitro. Graefes Arch Clin Exp Ophthalmol 250:507-14 |
| Tian, Baohe; Heatley, Gregg A; Filla, Mark S et al. (2010) Effect of H-7 on secondary cataract after phacoemulsification in the live rabbit eye. J Ocul Pharmacol Ther 26:533-9 |
