Pharmacologic inhibitors of PDGFR for the treatment of PVR

描述(由申请人提供)：作为临床科学家发展指导奖(K08)的获得者，我将能够直接在谢彭斯眼科研究所Andrius Kazlauskas博士的赞助下工作，追求将患者护理与研究相结合的职业目标。在一个以卓越的眼科研究而闻名的研究所，与经验丰富的科学家进行全职工作和合作，将使我获得必要的基本技能，以进一步了解和研究涉及眼部疾病，特别是增殖性玻璃体视网膜病变(PVR)的分子机制。这将补充和进一步扩大我以前培训奠定的基础，并给我所需的工具，使我在未来几年成为我所在领域的一名富有成效和重要的贡献者。这项资助中提出的工作旨在促进我们对PVR和血小板衍生生长因子(PDGF)在这种疾病中所起的作用的了解。更重要的是，这使我们能够寻找治疗这种人类致盲疾病的潜在药物。为此，本建议重点研究PDGFR抑制剂STI571在兔PVR模型中的疗效和毒性。其他试剂也将在上市时进行测试和比较。这项工作的结果可能会导致未来的临床试验，可能会改变我们在人类身上治疗这种疾病的方式，并改善患有这种潜在致盲并发症的患者的视力恢复预后。此外，通过这项工作获得的知识可能会增加对其他与纤维增殖有关的致盲眼内疾病的理解和未来的治疗方法，如早产儿视网膜病变(ROP)、增殖性糖尿病视网膜病变(PDR)以及视网膜下纤维化和盘状瘢痕形成，如黄斑变性(AMD)。

DESCRIPTION (provided by applicant): As a recipient of a Mentored Clinical Scientist Development Award (K08) I would be able to work directly under the sponsorship of Dr. Andrius Kazlauskas at the Schepens Eye Research Institute in my goal of pursuing a career that combines patient care with research. Working and collaborating on a full-time basis with experienced scientists in an Institute known for its excellence in eye research, will allow me to acquire the basic skills necessary to further understand and investigate molecular mechanisms involved in the pathophysiology of ocular disease, and in particular proliferative vitreoretinopathy (PVR). This would complement and further expand the foundation laid by my prior training, and give me the tools needed to become a productive and significant contributor to my field through years to come. The work proposed in this grant is meant to advance our understanding PVR and the role that platelet derived growth factor (PDGF) plays in this disease. More importantly, allow us to search for potential agents for the treatment of this blinding condition in humans. To this end, this proposal focuses on studying the efficacy and toxicity of STI571, a PDGFR inhibitor, in a rabbit model of PVR. Other agents will also be tested and compared as they become available. The results from this work could potentially lead to future clinical trials that could change how we treat this disease in humans, and improve the prognosis for visual recovery for patients who develop this potentially blinding complication. Furthermore, the knowledge acquired through this work could lead to increased understanding of and future therapies for other blinding intraocular disorders involving fibrous proliferation, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and subretinal fibrosis and disciform scar formation such as seen in macular degeneration (AMD).