新型叶绿素衍生物的制备及其抗视网膜黄斑变性作用研究

Retinal Macular degeneration is an irreversible decrease or loss of vision disease caused by retinal pigment epithelial cell degeneration. It is one of the most difficult eye disease recognized by the international ophthalmology community.. Photodynamic therapy (PDT) is a promising retinal macular degeneration treatment in which a photosensitizing drug accumulates in tissues and is subsequently activated by visible light of an appropriate wavelength matched to the absorption spectrum of the photosensitizer. Following the absorption of light, the photosensitizer is transformed from its ground state to the excited state. The excited drug leads to cytotoxicity by way of type I and type II reactions. Type I reaction involves the production of radicals resulting from the activated sensitizer reacting with plasma membrane or other molecules. The radicals interact with oxygen to produce oxygenated products. Type II reaction involves generation of singlet oxygen upon energy transfer from the activated sensitizer to oxygen. The ratio between type I and type II reactions depends on the type of photosensitizer used, the concentrations of oxygen and target substrate, and the binding affinity of the photosensitizer for its target substrate. One important feature of PDT is that it provides a selective therapeutic effect sparing surrounding normal tissue by preferential accumulation of the photosensitizer in the tissue and light irradiation restricted to the target tissue. Due to minimal invasiveness of PDT, it has been used to treat age-lated macular degeneration. With the development of new photosensitizers and the advancement of fiber optic delivery devices, substantial research has been invested in exploring their potential application in PDT of retinal macular degeneration ..Here series of novel chlorins will be designed and synthesized. Their photodynamic anti-age-lated effects in vitro and in vivo will be evaluated. The photochemical and photobiological mechanism and the structure-activity relationships will also be investigated.These work will be of great value to the development of new photodynamic drugs, and to the use of PDT in clinics.

视网膜黄斑变性是视网膜色素上皮细胞变性造成的一种不可逆性视力下降或丧失的疾病，严重威胁老年人的视功能，是国际眼科界公认的最难治疗的眼病之一。.近年来，光动力治疗视网膜黄斑变性已引起广泛关注，初步研究表明该法疗效确切、创伤小、恢复快，有望成为治疗视网膜黄斑变性的主要疗法之一。.本研究通过制备一系列新型叶绿素等二氢卟吩化合物，在细胞与整体动物水平测定其对视网膜黄斑变性的治疗作用，测定其分布情况，研究其微观光化学作用机理，研究其抗视网膜黄斑变性作用机理，提供具有自主知识产权、定向、高效、价廉、无皮肤光毒作用的视网膜黄斑变性治疗候选新药，促进光动力疗法在临床上的推广应用。

视网膜黄斑变性是视网膜色素上皮细胞变性造成的一种不可逆性视力下降或丧失的疾病，严重威胁老年人的视功能，是国际眼科界公认的最难治疗的眼病之一。近年来，光动力治疗视网膜黄斑变性已引起广泛关注，初步研究表明该法疗效确切、创伤小、恢复快，有望成为治疗视网膜黄斑变性的主要疗法之一。. 本研究通过研制系列叶绿素等二氢卟吩单体化合物，对其光化学与光生物学性能进行了研究，测定了新化合物的分布情况，并分别在细胞与动物水平研究了化合物对视网膜黄斑变性的光动力治疗效果及其对脉络膜新生血管的封闭作用机制，研究了构效关系，从而提供治疗视网膜黄斑变性新药候选化合物，建立了视网膜黄斑变性高效的治疗方法，促进光动力疗法在临床上的推广应用。