PROTECTION OF THE RETINA AGAINST OXIDATIVE DAMAGE

保护视网膜免受氧化损伤

• 批准号: 6180081
• 负责人: RICHARD C HUNT
• 金额: $ 20.77万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180081
• 关键词: DNA footprinting; RNase protection assay; angiogenesis; antioxidants; enzyme activity; enzyme deficiency; enzyme induction /repression; free radical oxygen; gel mobility shift assay; genetically modified animals; heme; heme oxygenase; in situ hybridization; laboratory mouse; laboratory rat; neuroprotectants; oxidative stress; retinopathy of prematurity; transcription factor; western blottings

DESCRIPTION (Adapted from applicant's abstract): The retina of the premature infant is believed to be highly susceptible to damaging influences of oxygen. The reason for this susceptibility is unknown, but it may be the result of an incompletely developed retinal antioxidant system. It has been shown that one antioxidant, heme oxygenase-1 (HO-1), is not developed in the rat until close to the time of birth. It is planned to investigate the kinetics of expression of the major antioxidant systems in the embryonic and neonatal rat retina using in situ hybridizations and ribonuclease protection assays. The importance of HO-1 in protection against oxidative stress will be determined in transgenic mice in which the HO-1 gene is under the control of a switchable promotor and in HO-1 knockout mice. Control of the expression of this enzyme a few days prior to birth will be studied using transgenic mice that carry a reporter gene coupled to the HO-1 promotor. Progressive deletion of the control regions of the promotor will allow the identification of the control sites and transcription factors involved. The identification of such factors may allow the elucidation of signaling pathways that mediate the correct expression of HO-1.

描述（改编自申请人的摘要）：据信早产儿的视网膜非常容易受到氧气的破坏性影响。这种易感性的原因尚不清楚，但可能是视网膜抗氧化系统发育不完全的结果。研究表明，一种抗氧化剂，血红素加氧酶-1 (HO-1)，直到接近出生时才在大鼠体内形成。计划利用原位杂交和核糖核酸酶保护测定来研究胚胎和新生大鼠视网膜中主要抗氧化系统的表达动力学。 HO-1 在防止氧化应激方面的重要性将在 HO-1 基因受可切换启动子控制的转基因小鼠和 HO-1 敲除小鼠中确定。将使用携带与 HO-1 启动子偶联的报告基因的转基因小鼠来研究出生前几天对该酶表达的控制。启动子控制区的逐步删除将允许识别所涉及的控制位点和转录因子。这些因子的鉴定可能有助于阐明介导 HO-1 正确表达的信号通路。