In Vivo Ocular Angiogenesis Assay

体内眼部血管生成测定

• 批准号: 6876292
• 负责人: MARYANN L HALDI
• 金额: $ 15.66万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876292
• 关键词: alternatives to animals in research; angiogenesis; bioassay; drug screening /evaluation; embryogenesis; eye circulation; eye pharmacology; macular degeneration; monoclonal antibody; technology /technique development; zebrafish

Eye diseases related to neovascularization are: diabetic retinopathy and age-related macular degeneration, the two leading causes of adult blindness in developed countries; retinopathy of prematurity, the major cause of vision loss in premature infants; and corneal neovascularization due to corneal injury, infection, or failed transplantation. Using zebrafish, this SBIR aims to develop a quantitative in vivo assay for assessing drug effects on ocular neovascularization. This SBIR will also investigate embryogenesis and patterning. Zebrafish is uniquely suitable for screening drugs that block ocular neovascularization. The pattern of vessels on the surface of the zebrafish eye is tightly regulated, permitting easy visual screening for drug effects. The transparency of the embryo permits identification of defects in vessel development in the eye and throughout the embryo. Rapid ex-utero development of the zebrafish allows drug administration, either by direct incubation in fish water (for small molecule) or injection (for large molecules such as RNA, DNA, morpholinos oligonucleotides, or antibodies). Zebrafish embryos do not require blood for normal development during the first week, obtaining sufficient oxygen by diffusion. Therefore, it is possible to perform treatment of the whole animal with anti-angiogenic drugs. The proposed zebrafish assay will facilitate development of therapeutic drugs to treat eye diseases caused by neoangiogenesis.

与新生血管形成相关的眼部疾病有：糖尿病性视网膜病变和年龄相关性黄斑变性，这是发达国家成人失明的两个主要原因；早产儿视网膜病变，是早产儿视力丧失的主要原因；以及由于角膜损伤、感染或移植失败导致的角膜新生血管形成。该 SBIR 旨在使用斑马鱼开发一种定量体内测定法，以评估药物对眼部新生血管形成的影响。该 SBIR 还将研究胚胎发生和模式。 斑马鱼特别适合筛选阻断眼部新生血管形成的药物。斑马鱼眼睛表面的血管图案受到严格控制，可以轻松地通过视觉筛选药物效应。胚胎的透明度允许识别眼睛和整个胚胎中血管发育的缺陷。斑马鱼的快速体外发育允许通过直接在鱼水中孵育（对于小分子）或注射（对于大分子，例如RNA、DNA、吗啉寡核苷酸或抗体）来给药。斑马鱼胚胎在第一周内不需要血液来正常发育，通过扩散获得足够的氧气。因此，可以用抗血管生成药物对整个动物进行治疗。拟议的斑马鱼测定将促进治疗药物的开发，以治疗由新生血管生成引起的眼部疾病。