Arjun Jaitli

Graduation Semester and Year

2021

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Liping Tang

Abstract

Posterior capsule opacification (PCO) is the most common complication associated with intraocular lens (IOL) implantation. Unfortunately, current in vitro models cannot be used to assess the potential of PCO due to their failure to simulate posterior curvature of the lens capsule (LC), contradicting observations, different testing conditions and inherent challenges associated with use of human capsular bag models, cells and other tissue substrates. To overcome such a challenge, a new system to study IOL: LC interaction and potentially predict PCO was developed in this effort. It is believed that the interactions between an IOL and the lens capsule (LC) may influence the extent of PCO formation. Specifically, strong adhesion force between an IOL and the LC may impede lens epithelial cell migration and proliferation and thus reduce PCO formation. For Aim 1, to measure the adhesion force between an IOL and LC, a new in vitro model was established with simulated LCs and a custom-designed micro-force tester. A method to fabricate simulated LCs was developed by imprinting IOLs onto molten gelatin to create simulated three dimensional (3D) LCs with curvature resembling the bag-like structure that collapses on the IOL post implantation. An in vitro system that can measure the adhesion force reproducibly between an IOL and LC with a resolution of ~ 1 μN was established in this study. During system optimization, the 10% high molecular weight gelatin produced the best LC with the highest IOL-LC adhesion force with all test lenses that were fabricated from acrylic foldable, polymethylmethacrylate (PMMA) and silicone materials. Test IOLs exerted different adhesion force with the 3D simulated LCs in the following sequence: acrylic foldable IOL > silicone IOL > PMMA IOL. These results were in good agreement with the clinical observations associated with PCO performance of IOLs made of the same materials. In Aim 2, using the aforementioned custom designed micro force tester, the influence of temperature and incubation time on the adhesion force between IOLs and LCs was investigated. Using this 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 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 both the 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. In Aim 3, the role of fibronectin in mediating the adhesion between different IOL materials and the simulated lens capsule was examined. Briefly, a range of fibronectin concentrations were first studied using an acrylic foldable IOL that is believed to interact with fibronectin in vivo to create a strong bond between the lens capsule and the IOL surface. Our results indicated that the adhesion of the acrylic foldable IOLs increased significantly in the presence of Fibronectin. Using surface contact angle measurements, we observed that the adsorption of fibronectin on acrylic foldable groups creates a hydrophilic layer on the surface of the acrylic foldable group that may increase its adhesion with the lens capsule. Our dye infusion study further confirmed this tight binding by showing reduced dye penetration in acrylic foldable IOLs in the presence of fibronectin. However, the presence of fibronectin in lens capsules did not affect the adhesion for silicone and PMMA materials. Next, the influence of surface modification of the acrylic foldable IOLs on its adhesion characteristics was also assessed by modifying them with Poly(ethyleneglycol) (PEG) and Di(ethyleneglycol) dimethyl ether (Digylme). Our results indicated that surface modification of acrylic foldable IOLs with PEG did not affect their adhesive forces and interaction with fibronectin, which are both well known material properties of the Acrysof lens that contribute to its excellent PCO performance in the clinic. However, surface modification of the acrylic lenses with Digylme showed drastically reduced adhesion forces with the capsule, and high rate of dye penetration making it an undesirable candidate as a potential hydrophilic coating for IOL materials.

Keywords

Intraocular lens, Lens capsule, Adhesion force, Posterior capsule opacification, In vitro model, Gelatin, 3D model

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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