Pre-mRNA Interference of VEGF Pathways in Ocular Angiogenesis

描述（由申请人提供）： Ambati博士计划继续研究破坏细胞内新血管形成的途径;这将增强并可能超越目前的细胞外阻断疗法。通过使用新技术来破坏基因信息传递系统，该系统传达形成新血管的方向，该提案有可能推进各种致盲疾病的治疗，包括角膜损伤（眼睛的前部），糖尿病视网膜损伤和黄斑变性。这可以转化为改善那些眼睛受伤并需要角膜移植的退伍军人的结果（因为对抗血管形成对角膜透明度和防止角膜移植排斥至关重要），以及改善患有糖尿病视网膜病变和黄斑变性的退伍军人的视力，这是老年退伍军人失明的主要原因。此外，这种通过靶向细胞内的关键遗传事件来对抗血管形成的方法可能对癌症有重大的有益应用。 公共卫生相关性： 与退伍军人健康相关：角膜新生血管是眼损伤的一种威胁视力的并发症，由弹片、简易爆炸装置（IED）或风沙造成。角膜新生血管的消退有望促进持续战斗眼损伤的士兵或退伍军人的视力恢复。在100多万低视力（定义为低于20/70）的退伍军人中，约有一半是由于黄斑变性或糖尿病。退伍军人管理局在每个低视力病例的康复治疗上花费> 43，000美元[59]，在Lucentis治疗上每个患者每年花费> 30，000美元，Lucentis是退伍军人管理局唯一批准的新生血管性AMD治疗方法。该建议的细胞内抑制VEGF的新方法可能有望转化为更好的治疗角膜损伤和黄斑变性。它最终可能有助于治疗癌症和糖尿病视网膜病变。

DESCRIPTION (provided by applicant): Dr. Ambati plans to continue his research into disrupting pathways of new blood vessel formation within cells; this will augment and possibly transcend the current therapies of blockade outside the cell. By using novel techniques to disrupt the gene messaging systems which communicate directions to form new blood vessels, this proposal has the potential of advancing therapies for a variety of blinding conditions, including injury to the cornea (the front part of the eye), diabetes damage to the retina, and macular degeneration. This could translate into improved outcomes for veterans who sustain eye injury and require corneal transplantation (as fighting blood vessel formation is essential to corneal transparency and preventing corneal transplant rejection), as well as improved vision for veterans with diabetic retinopathy and macular degeneration, which are the leading cause of blindness among older veterans. Further, this approach of fighting blood vessel formation by targeting key genetic events within the cell could have major beneficial applications to cancer. PUBLIC HEALTH RELEVANCE: Relevance to Veterans' Health: Corneal neovascularization is a sight-threatening complication of ocular injury, from shrapnel, improvised explosive devices (IEDs), or blowing sand. Regression of corneal neovascularization will hopefully facilitate vision restoration in soldiers or veterans who sustained combat eye injuries. Of the more than 1 million veterans with low vision (defined as less than 20/70), about half are due to macular degeneration or diabetes. The VA spends >$43,000 per low vision case for rehabilitation [59] and >$30,000 per year per patient on LucentisTM therapy, the only approved treatment in the VA for neovascular AMD. This proposal's novel approaches to inhibiting VEGF intracellularly may hopefully translate into better treatment of corneal injury and macular degeneration. It may eventually be of relevance in helping treatment of cancer & diabetic retinopathy.