Reduction of the scleral adhesion of tenon fibroblasts

青光眼是视神经的一种慢性进行性疾病，是导致不可逆失明的主要原因。降低眼压（IOP）是目前唯一的循证治疗。如果通过药物治疗不能充分实现这一点，切口手术可以为结膜下间隙的水提供流出通道（青光眼滤过手术，即小梁切除术）。治疗的成功很大程度上受到术后伤口愈合的限制，这是一个实际的生理过程，在这种情况下会导致人工瘘管的瘢痕和失败。到目前为止，青光眼滤过手术的术后伤口愈合受到细胞毒性药物的修饰和抑制，从而增加了视力威胁并发症的风险。迄今为止，选择性干扰活化的促炎细胞因子的尝试尚未成功。本项目建议的目的是防止由肌腱成纤维细胞阻塞所形成的瘘管形成粘连疤痕组织。疤痕组织的缺乏附着力保证结膜下的液体流动，而不考虑细胞因子的改变。长期成功的瘘管（即低IOP）因此改善了患者。用高分子材料制成的巩膜涂层将用于此目的。在体内相容的条件下，这些聚合网络通过共价键固定在巩膜组织上。目的是局部防止所有类型的细胞粘附在聚合物材料上。生理性的，术后的疤痕将无法通过粘连到下面的组织来阻塞手术瘘管。在这个项目的第一部分，方法和材料在体外开发，并在体内动物模型中进行生物相容性测试。该项目的第二部分将致力于将结果转化为人类应用。

Glaucoma is a chronic progressive disease of the optic nerve, a leading cause of irreversible blindness. The reduction of intraocular pressure (IOP) is currently the only evidence-based treatment. If this cannot be achieved sufficiently by medication, incisional surgery creates an outflow pathway for the aqueous to the subconjunctival space (glaucoma filtering surgery, i.e. trabeculectomy). The success of the treatment is strongly limited by the postoperative wound healing, an actually physiological process that, in this situation leads to scarring and failure of the artificial fistula. So far, postoperative wound healing in glaucoma filtration surgery is modified and suppressed by cytotoxic agents with, in turn, increased risk for sight-threatening complications. Attempts to selectively interfere with activated pro-inflammatory cytokines have been unsuccessful so far. The aim of this project proposal is to prevent the formation of adhesive scar tissue formed by tenon-fibroblasts occluding the created fistula. The lack of adhesion of scar tissue guarantees flow of aqueous liquid under the conjunctiva, irrespective of cytokine alterations. Long term success of fistulation (meaning low IOP) is thereby improved for the patient. Scleral coatings made of polymeric materials are to be developed for this purpose. These polymeric networks are fixed on the scleral tissue by covalent bonds under in-vivo compatible conditions. The aim is to locally prevent all types of cellular adhesion on the polymeric material. Physiologic, postoperative scarring will then not be able to occlude the surgical fistula by adhesion to the underlying tissue. In the first part of this project, methods and materials are developed in-vitro and biocompatibility is tested in an in-vivo animal model. The second part of the project will then aim to transfer the results to human application.