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| Ophthalmology |
Transplantation of iris pigment epithelial cells (IPE) and retinal pigment epithelial cells (RPE) is being studied as a potential treatment for Age-Related Macular Degeneration (AMD) and other maculopathies. Although transplanted IPE and RPE have been shown to survive after injection into the subretinal space, their inability to spontaneously form an organized monolayer and maintain their phenotype may impede their ability to perform the functions of native RPE. To address these challenges, we are investigating whether anterior lens capsule or other biomaterials can be used as a substrate for transplanting pigment epithelium cells into the subretinal space as well as a patch for Bruch's membrane.
Testing the properties of lens capsule revealed that the patterning of inhibitory molecules is required for organizing cells on lens capsule. Exhibiting good stability, poly(vinyl alcohol) (PVA) was found to prevent cell adhesion and spreading for at least one month on lens capsule. Using microcontact printing, we can mimic the natural RPE structure by directing cells to adhere selectively. Currently, RPE cells have been confined to circular and hexagonal shapes using PVA as an inhibitor with separations of only a few microns. This spacing is designed to allow cells to form tight junctions with neighbors.
 Fluorescence image of PVA-patterned human lens capsule. |
 Brightfield image of human RPE cells cultured on PVA-patterned lens capsule. |
Bright-field image of PLGA (stained with sulforhodamine acid chloride)
Furthermore, it is difficult to implant lens capsule into the subretinal space due to its tendency to curl up on itself, especially in an aqueous environment, thus giving it very poor surgical handling. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible, biodegradable synthetic polymer that has several established uses in medicine. PLGA can be synthesized to form thin but sufficiently rigid films. While others have tried culturing cells on PLGA alone, this does not solve the problem of choroidal neovascularization since PLGA dissolves with time and does not create a patch effect on the Bruch's membrane. We are evaluating the usefulness of PLGA as a solid substrate to improve the surgical handling of lens capsule during subretinal implantation.
- Principal Investigator:
Mark Blumenkranz, MD. - Collaborators:
Stacey Bent, PhD. (Chem. Eng.)
Roopa Dalal, MSc.
Michael Marmor, MD.
