Photopolymerization has provided a powerful tool for tissue engineering through localized synthesis of therapeutic materials in situ. To date, strategies to create photopolymerized networks on the surface of a tissue, such as the inner lumen of a blood vessel or on the fracture surface of a bone have received the most attention. The proposal will demonstrate a clinically-relevant strategy to create a reinforcing network within a given tissue-the sclera-to halt pathological deformation of that tissue in degenerative myopia. An interdisciplinary team with expertise in ophthalmology, polymer chemistry, tissue viscoelastic properties and light delivery will pioneer this new strategy for engineering the mechanical properties of tissues in situ, particularly in the eye. The objective of this proposal is to demonstrate that photopolymerization of an FDA approved macromer (PEG-diacrylate) can be induced in the sclera to affect an adequate change in mechanical integrity of the sclera to prevent elongation of the globe of the eye in vitro. To determine the feasibility of enhancing the mechanical integrity of the sclera and preventing abnormal elongation of the eye in degenerative myopia we have the following goals: (1) Strengthen tissue sections in vitro using photopolymerization of PEGDM, (1.a) Increase water solubility and biocompatibility of photoinitiators, (1.b) Dose-response characteristics will be determined that relate treatment variables (PEG length, choice of methacrylate vs. acrylate end groups, photoinitiator structure and concentration, diffusion time and irradiation time) to the quantitative change in mechanical properties of sections of sclera characterized pre-and post-treatment in vitro; (2) Demonstrate photopolymerization treatment effectively stabilizes ocular shape in vitro using an elevated intraocular pressure model; and (3) Evaluate cytotoxicity of photopolymerized PEGDM(A) in cell culture and its biocompatibility in a rabbit model. To achieve these aims, we combine unique capabilities developed at Caltech with Visdex's expertise in light-delivery and photopolymerization in the eye. Significantly, methods to quantify mechanical properties of ocular tissues and correlate them with in vitro deformation behavior of the globe of the eye have already been established at Caltech. The proposed research will result in a therapeutic platform for treating diseases associated with inadequate mechanical stability of tissue, setting the stage for in vivo studies of the treatment of degenerative myopia in Phase II. ? ? ? ?
| Mattson, Matthew S; Huynh, Joyce; Wiseman, Meredith et al. (2010) An in vitro intact globe expansion method for evaluation of cross-linking treatments. Invest Ophthalmol Vis Sci 51:3120-8 |
