Retinal Mechanisms of Refractive Development

视网膜屈光发育机制

• 批准号: 10400053
• 负责人: Machelle T. Pardue
• 金额: $ 8.08万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10400053
• 关键词: Address; Adult; Affect; Automobile Driving; Cell physiology; Characteristics; Child; Childhood; Cone; Data; Detection; Development; Dopamine; Environment; Exposure to; Eye; Eye diseases; Fostering; Funding; Gap Junctions; Goals; Growth; Image; Intervention; Knock-out; Knowledge; Light; Lighting; Measurement; Measures; Mus; Myopia; Neuromodulator; Organism; Outcome; Pathway interactions; Photoreceptors; Photosensitivity; Population; Predisposition; Prevalence; Proteins; Reporting; Research; Retina; Retinal Ganglion Cells; Risk Factors; Rod; Role; Signal Pathway; Signal Transduction; Sunlight; Testing; Therapeutic Intervention; Time; Transgenic Mice; Vertebrate Photoreceptors; Vision; Visual; Wild Type Mouse; connexin 36; deprivation; designer receptors exclusively activated by designer drugs; effective therapy; experimental study; innovation; intervention effect; lens; mouse model; mutant; novel therapeutic intervention; prevent; protective effect; response; sensor; therapeutic development; transmission process; visual stimulus

Abstract The rapid increase in myopia prevalence over the last 30 years suggests a role for the environment in controlling refractive development. Accumulating evidence suggests that ambient light (e.g. sunlight) affects eye growth during childhood by dopamine signaling. However, the characteristics of visual stimuli and underlying retinal signals that regulate refractive development remain elusive. In this proposal, the knowledge gap concerning whether retinal “gain adjustment” pathways for ambient irradiance may alter myopia susceptibility will be addressed. Preliminary data shows that both dim and bright light are protective for lens- induced myopia in mice and that myopic children spend less time in both dim and bright light. Furthermore, dopamine activity is differentially modulated by an interaction effect of exposure to variable ambient lighting and lens defocus. Thus, the hypothesize that retinal “gain adjustment” to ambient light determines an organism’s susceptibility to myopia through dopamine signaling will be tested. It is proposed that retinal detection of irradiance occurs through non-classical retinal pathways that have been reported to detect light across a broad range of ambient conditions from starlight to sunlight. This proposal will determine which photoreceptor pathways modulate the protective effects of scotopic and photopic light on lens induced myopia and the role of dopamine signaling by pursuing three specific aims using mouse models. Aim 1 will evaluate if rod pathway stimulation drives dopamine release and decreases myopic refractions under dim and bright ambient conditions. Aim 2 will investigate if retinal transmission through Cx36 gap junctions provides protective effects for LIM in dim and bright light via increased dopamine release. Aim 3 will determine whether ipRGCs modulate refractive development by detecting visual stimuli under a full range of ambient conditions. The expected outcomes will increase our knowledge of basic retinal dopamine signaling and further elucidate the mechanisms underlying myopic eye growth. These results are expected to foster the development of new therapeutic interventions for the growing number of myopic children.

摘要