Experimental models for posterior capsule opacification research

Abstract

Millions of people worldwide are blinded due to cataract formation. At present the only means of treating a cataract is through surgical intervention. A modern cataract operation involves the creation of an opening in the anterior lens capsule to allow access to the fibre cells, which are then removed. This leaves in place a capsular bag that comprises the remaining anterior capsule and the entire posterior capsule. In most cases, an intraocular lens is implanted into the capsular bag during surgery. This procedure initially generates good visual restoration, but unfortunately, residual lens epithelial cells undergo a wound-healing response invoked by surgery, which in time commonly results in a secondary loss of vision. This condition is known as posterior capsule opacification (PCO) and exhibits classical features of fibrosis, including hyperproliferation, migration, matrix deposition, matrix contraction and transdifferentiation into myofibroblasts. These changes alone can cause visual deterioration, but in a significant number of cases, fibre differentiation is also observed, which gives rise to Soemmering's ring and Elschnig's pearl formation. Elucidating the regulatory factors that govern these events is fundamental in the drive to develop future strategies to prevent or delay visual deterioration resulting from PCO. A range of experimental platforms are available for the study of PCO that range from in vivo animal models to in vitro human cell and tissue culture models. In the current review, we will highlight some of the experimental models used in PCO research and provide examples of key findings that have resulted from these approaches.

Dual function of TGFβ in lens epithelial cell fate: implications for secondary cataract

“…, 2005; Walker and Menko, 2009). TGFβ is the only factor known to be able to induce lens cells to undergo epithelial–mesenchymal transition (EMT) into α−smooth muscle actin (αSMA)–expressing myofibroblasts in the three major in vitro systems heretofore used to study PCO, namely weanling rat lens central epithelial explants, lens epithelial cell–derived cell lines, and capsular bags prepared from human cadaver lenses (Wormstone and Eldred, 2016). Overexpression of a self-activating form of TGFβ in the intact rodent lens in vivo results in the formation of ASC containing fibrotic, myofibroblastic cells (Srinivasan et al.…”

“…The primary inducer of epithelial-to-fiber cell differentiation in the intact lens during normal lens development is fibroblast growth factor (FGF), which is found in levels sufficient to promote fiber cell differentiation in the vitreous humor but not in the aqueous humor (reviewed in Lovicu and McAvoy, 2005; Robinson, 2006), It has generally been assumed, but never experimentally proven, that the high levels of FGF in the vitreous humor are also responsible for the differentiation of residual lens epithelial cells into fiber cells after cataract surgery (Wormstone et al. , 2009; Wormstone and Eldred, 2016; Shirai et al. , 2014).…”

In Vitro Evaluation of the Effects of Intraocular Lens Material on Lens Epithelial Cell Proliferation, Migration, and Transformation

“…4,7,8 As the total removal of these LECs is not possible using current ophthalmological techniques, many laboratories have instead focused on preventing PCO by exploiting the characteristics of the IOL in terms of the composition of the biomaterial as well as the edge design. 9 In fact, it is well documented that implantation of IOLs utilizing a sharp edge design results in a lower level of PCO-related LEC migration. 10,11 Furthermore, numerous clinical studies have been conducted to compare various IOL designs and material composition combinations.…”

Improving the drug development process by reducing the impact of adverse events: the case of cataracts considered

“…Equally, in terms of high throughput screening, human lens cell lines could provide a relatively cheap and efficient system and could serve as a possible predictor for the outcome of human clinical trials. Importantly such screening assays could flag early problems and so avoid needless animal usage and potentially adverse events in human clinical trials at least in so far as systemic compounds causing cataractogenic adverse events are concerned [16]. However, additional consideration should be made regarding the limited blood supply to the lens and the likelihood of specific agents entering the eye and accruing in the ocular humours that bathe the lens [2].…”