A 3D in vitro model for assessing the influence of intraocular lens: Posterior lens capsule interactions on lens epithelial cell responses.

Posterior Capsule Opacification (PCO), the most frequent complication of cataract surgery, is caused by the infiltration and proliferation of lens epithelial cells (LECs) at the interface between the intraocular lens (IOL) and posterior lens capsule (PLC). According to the "no space, no cells, no PCO" theory, high affinity (or adhesion force) between the IOL and PLC would decrease the IOL: PLC interface space, hinder LEC migration, and thus reduce PCO formation. To test this hypothesis, an in vitro hemisphere-shaped simulated PLC (sPLC) was made to mimic the human IOL: PLC physical interactions and to assess their influence on LEC responses. Three commercially available IOLs with different affinities/adhesion forces toward the sPLC, including Acrylic foldable IOL, Silicone IOL, and PMMA IOL, were used in this investigation. Using the system, the physical interactions between IOLs and sPLC were quantified by measuring the adhesion force and interface space using an adhesion force apparatus and Optical Coherence Tomography, respectively. Our data shows that high adhesion force and tight binding between IOL and sPLC contribute to a small interface space (or "no space"). By introducing LECs into the in vitro system, we found that, with small interface space, among all IOLs, acrylic foldable IOLs permitted the least extent of LEC infiltration, proliferation, and differentiation (or "no cells"). Further statistical analyses using clinical data revealed that weak LEC responses are associated with low clinical PCO incidence rates (or "no PCO"). The findings support that the in vitro system could simulate IOL: PLC interplays and predict IOLs' PCO potential in support of the "no space, no cells, no PCO" hypothesis.

Role of fibronectin and IOL surface modification in IOL: Lens capsule interactions.

Posterior Capsule Opacification (PCO) is one of the most common complications of cataract surgery. While studies have shown that IOL material properties and fibronectin adsorption may affect IOL-induced PCO in the clinical setting, the mechanism governing such interactions is not totally understood. Since strong adhesion forces between IOLs and posterior capsules (PCs) have been shown to impede cell infiltration and thus reduce PCO formation, this study was designed to assess whether fibronectin adsorption and IOL material properties would impact the IOL:PC adhesion force and cell infiltration using a PCO predictive in vitro model and a macromolecular dye imaging model, respectively. Our results showed that fibronectin adsorption significantly increased the adhesion forces and reduced simulated cell infiltration between acrylic foldable IOLs and the PC at physiological temperature in comparison to fibronectin-free controls. This fibronectin-mediated strong IOL: PC bond may be contributing to low PCO rates in the clinic for acrylic foldable IOLs. In addition, acrylic foldable IOLs coated with Di(ethylene glycol) (Diglyme), a hydrophilic coating known to reduce protein adsorption, was tested for its ability to alter adhesion force and cell infiltration. We observed that IOLs coated with Diglyme coating greatly reduced surface hydrophobicity and fibronectin adsorption of acrylic foldable IOLs. Furthermore, Diglyme coated IOLs showed significantly reduced adhesion force and increased simulated cell infiltration at the IOL:PC interface. The overall results support the hypothesis that IOL surface properties and their ability to adsorb fibronectin may have great impact on the IOL:PC adhesion force. A tight binding between IOLs and PC may contribute to the reduction of cell infiltration and thus the PCO incidence rate in the clinic.

Effect of time and temperature-dependent changes of IOL material properties on IOL: Lens capsule interactions.

Posterior Capsule Opacification (PCO) is the most common complication associated with Intraocular Lens (IOL) implantation. Based on the assumption that the interactions between an IOL and the lens capsule (LC) may influence the extent of PCO formation, a new in vitro model was developed to quantify the adhesion force of an IOL to simulated LC using a custom-designed micro-force tester. Using this system, we examined the influence of temperature (room temperature vs. body temperature) and incubation time (0 vs. 24 h) on the adhesion force between IOLs and LCs. The results show that, in line with clinical observations of PCO incidence, the adhesion force increased at body temperature and with increase in incubation time in the following order, Acrylic foldable IOLs > Silicone IOLs > PMMA IOLs. By examining the changes of surface properties as a function of temperature and incubation time, we found that acrylic foldable IOLs showed the largest increase in their hydrophilicity and reported the lowest surface roughness in comparison to other IOL groups. Coincidentally, using a newly established macromolecular dye imaging system to simulate cell migration between IOLs and LC, we observed that the amount of macromolecular dye infiltration between IOLs and LCs was in the following order: PMMA IOLs > Silicone IOLs > Acrylic foldable IOLs. These results support a new potential mechanism that body temperature, incubation time, surface hydrophilicity and smoothness of IOLs greatly contribute to their tight binding to LCs and such tight binding may lead to reduced IOL: LC space, cell infiltration, and thus PCO formation.