Pre-mRNA Interference of VEGF Pathways in Ocular Angiogenesis

眼部血管生成中 VEGF 通路的前 mRNA 干扰

• 批准号: 7796909
• 负责人: BALAMURALI K AMBATI
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7796909
• 关键词: Affect; Age related macular degeneration; Albumins; Alternative Splicing; Binding; Blindness; Blood Vessels; Bruch' s basal membrane structure; CCL2 gene; Cells; Choroid; Choroidal Neovascularization; Clinical; Code; Complication; Cornea; Corneal Injury; Corneal Neovascularization; Custom; Development; Devices; Diabetes Mellitus; Diabetic Retinopathy; Elements; Event; Exons; Exudative age-related macular degeneration; Eye; Eye Injuries; Eye Part; Fluorescein; Genes; Genetic; Graft Rejection; Health; Homing; Injury; Integrin alphaVbeta3; Introns; Keratoplasty; Label; Lasers; Length; Macular degeneration; Malignant Neoplasms; Masks; Membrane; Messenger RNA; Modeling; Mus; Oligonucleotides; Oligopeptides; Outcome; Pathway interactions; Patients; Plasmids; Posterior eyeball segment structure; Protein Isoforms; RGD (sequence); RNA Splicing; Regulation; Rehabilitation therapy; Research; Retina; Retinal Neovascularization; Silicon Dioxide; Sister; Soldier; Spliceosomes; Structure; System; Techniques; Technology; Testing; Tissues; Transcend; Translating; Trauma; Vascular Endothelial Growth Factor Receptor; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Veterans; Vision; Visual impairment; Wild Type Mouse; base; cancer therapy; combat; fighting; improved; mRNA Precursor; macula; nanoparticle; neovascular; novel; novel strategies; novel therapeutic intervention; ocular angiogenesis; prevent; public health relevance; receptor; receptor expression; restoration; retinal angiogenesis; retinal damage; small molecule

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.

描述(由申请人提供)： 安巴蒂博士计划继续他的研究，破坏细胞内新血管形成的途径；这将加强甚至可能超越目前的细胞外阻断疗法。通过使用新的技术来扰乱传递方向以形成新血管的基因信息系统，这一提议有可能推进各种失明疾病的治疗，包括角膜损伤(眼睛的前部)、糖尿病对视网膜的损害和黄斑变性。这可能会改善眼部受伤并需要角膜移植的退伍军人的预后(因为对抗血管形成对于角膜透明度和防止角膜移植排斥反应至关重要)，以及患有糖尿病视网膜病变和黄斑变性的退伍军人的视力改善，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基因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：角膜新生血管是眼部损伤的一种威胁视力的并发症，由弹片、简易爆炸装置(IED)或吹沙造成。角膜新生血管的消退有望促进遭受眼部战伤的士兵或退伍军人的视力恢复。在100多万视力低下(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LucentisTM疗法上每个患者每年花费30,000美元，这是退伍军人管理局批准的唯一治疗新生血管性AMD的方法。这项提案提出的细胞内抑制血管内皮生长因子的新方法有望转化为更好地治疗角膜损伤和黄斑变性。它可能最终对癌症和糖尿病视网膜病变的治疗有帮助。