Novel Treatment for Degenerative Myopia

描述（由申请人提供）：光聚合通过原位局部合成治疗材料为组织工程提供了一种强大的工具。迄今为止，在组织表面（例如血管的内腔或骨的断裂表面）上产生光聚合网络的策略受到了最多的关注。该提案将展示一种临床相关的策略，在特定组织巩膜内建立一个加强网络，以阻止退行性近视中该组织的病理变形。一个拥有眼科学、聚合物化学、组织粘弹性和光传递专业知识的跨学科团队将开创这种新策略，用于原位工程化组织的机械性能，特别是在眼睛中。本提案的目的是证明可在巩膜中诱导FDA批准的大分子聚合物（PEG-二丙烯酸酯）的光聚合，以影响巩膜机械完整性的适当变化，从而防止体外眼球地球仪伸长。为了确定增强巩膜的机械完整性和防止退行性近视中眼睛的异常伸长的可行性，我们有以下目标：（1）使用PEGDM的光聚合在体外强化组织切片，（1.a）增加光引发剂的水溶性和生物相容性，（1.b）将确定与治疗变量相关的剂量反应特征（PEG长度，甲基丙烯酸酯与丙烯酸酯端基的选择，光引发剂结构和浓度，扩散时间和照射时间）对体外处理前后表征的巩膜切片的力学性质的定量变化的影响;（2）使用升高的眼内压模型证明光聚合处理在体外有效地稳定眼睛形状;和（3）评价光聚合的PEGDM（A）在细胞培养物中的细胞毒性及其在兔模型中的生物相容性。为了实现这些目标，我们将加州理工学院开发的联合收割机独特能力与Visdex在眼睛中的光传递和光聚合方面的专业知识相结合。值得注意的是，加州理工学院已经建立了量化眼组织的机械特性并将其与眼睛的地球仪的体外变形行为相关联的方法。拟议的研究将产生一个治疗平台，用于治疗与组织机械稳定性不足相关的疾病，为II期退行性近视治疗的体内研究奠定基础。

DESCRIPTION (provided by applicant): 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.