Graduation Semester and Year
2022
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Biomedical Engineering
Department
Bioengineering
First Advisor
Liping Tang
Abstract
ABSTRACT: Posterior Capsule Opacification (PCO) is the most common complication associated with Intraocular Lens (IOL) implantation. The disease is caused by the infiltration and proliferation of Lens Epithelial Cells (LEC) into the interface between the IOL and Posterior Lens Capsule (PLC). The severity of these cell responses depends on a lot of factors like the IOL design, IOL material, and interaction between the IOL and the posterior lens capsule. While some studies have also shown that adsorption of certain proteins present in the PLC, like fibronectin, may affect IOL-induced PCO in the clinical setting, the mechanism governing such interactions is not totally understood. Based on the assumption that the interactions between an IOL and the PLC, along with the aforementioned factors, may influence the extent of PCO formation, a new in vitro model was developed to quantify the adhesion force of an IOL to simulated PLC using a custom-designed micro-force tester. For Aim 1, using the micro-force testing system, we examined the influence of temperature (room temperature vs. body temperature) and incubation time (0 vs. 24 hours) on the adhesion force between IOLs and PLCs. 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 PLC, we observed that the amount of macromolecular dye infiltration between IOLs and PLCs 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 PLCs and such tight binding may lead to reduced IOL: PLC space, cell infiltration, and thus PCO formation. In Aim 2, a study was designed to assess whether fibronectin adsorption and IOL material properties would impact the IOL: PLC 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 PLC at physiological temperature in comparison to fibronectin-free controls. This fibronectin mediated strong IOL: PLC 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: PLC interface. The overall results support the hypothesis that IOL surface properties and their ability to adsorb fibronectin may have great impact on the IOL: PLC adhesion force. A tight binding between IOLs and PLC may contribute to the reduction of cell infiltration and thus the PCO incidence rate in the clinic. For Aim 3, the “No space, no cell” hypothesis was studied, which states that an IOL with maximum contact with the PLC will leave no space for LEC infiltration and proliferation, has been used to explain this phenomenon. Although this hypothesis has been indirectly supported by in vivo studies, it has not been directly tested because current in vitro models lack the appropriate geometry to mimic the in vivo IOL and human PLC closure mechanism. Therefore, a 3D simulated PLC with similar geometry to the human PLC was developed to test the “No space, no cell” hypothesis. Optical Coherence Tomography (OCT) imaging showed the simulated PLC was able to reproduce in vivo closure mechanism. In addition, the “No space, no cell” hypothesis was directly tested by monitoring the infiltration and proliferation of LECs at the IOL: PLC interface. As expected, Acrylic IOL prevented the infiltration and proliferation of LECs while PMMA and Silicone IOLs permitted LEC infiltration and proliferation. Additionally, Acrylic IOL’s strong affinity for the simulated PLC induced the contact inhibition of LECs present at the interface. Overall, the simulated PLC was able to mimic IOL and human PLC interactions and the results supported the “No space, no cell” hypothesis.
Keywords
Intraocular lens, Posterior lens capsule, Posterior capsule opacification, Adhesion force, 3D in vitro model, Gelatin, Lens epithelial cells, Fibronectin, Optical coherence tomography.
Disciplines
Biomedical Engineering and Bioengineering | Engineering
License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Roy, Joyita, "An In vitro 3D Model to Investigate IOL: Posterior Lens Capsule Interactions on Lens Epithelial Cell Responses" (2022). Bioengineering Dissertations. 153.
https://mavmatrix.uta.edu/bioengineering_dissertations/153
Comments
Degree granted by The University of Texas at Arlington