Retinal Mechanisms of Refractive Development

视网膜屈光发育机制

• 批准号: 8204532
• 负责人: Machelle T. Pardue
• 金额: $ 30.67万
• 依托单位: EMORY UNIVERSITY
• 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 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8204532
• 关键词: American; Asians; Automobile Driving; Behavior Therapy; Biochemical; Biochemical Feedback; Biochemical Pathway; Blindness; Candidate Disease Gene; Cells; Characteristics; Chickens; Contrast Sensitivity; Country; Data; Defect; Detection; Development; Diagnosis; Dimensions; Dopamine; Down-Regulation; Environment; Epidemic; Eye; Eye Development; Feedback; Frequencies; Genes; Goggles; Growth; High Pressure Liquid Chromatography; Human; Hyperopia; Image; Interferometry; Intervention; Knowledge; Laboratories; Length; Measurement; Measures; Microarray Analysis; Modeling; Morphology; Mus; Mutant Strains Mice; Mutation; Myopia; Neurons; Operative Surgical Procedures; Optics; Pathway interactions; Photoreceptors; Population; Prevalence; Refractive Errors; Research; Retina; Retinal; Retinal Cone; Retinal Defect; Retinal Detachment; Risk; Role; SHFM1 gene; Signal Pathway; Signal Transduction; Testing; Transducin; Vertebrate Photoreceptors; Vision; Visual; Visual Accommodation; World Health Organization; base; cost; deprivation; design; insight; lens; mouse model; mutant; novel; prevent; programs; research study; response; retinal rods; transmission process; visual deprivation; visual feedback

Post-natal refractive development of the eye matches optical power with axial length to focus the visual image onto the photoreceptors. When successful, the eye reaches emmetropia or zero refractive error. However, ~25% of the US population develops myopia while only 10% develop hyperopia. The prevalence of myopia has reached near epidemic proportions in Asian countries. Progressive myopes and high myopes have increased risk of retinal detachment and blindness. While ~$3.9 billion dollars was spent in 2001 on refractive corrections for distance vision (not including the cost of nearly 1 million refractive surgeries performed), no treatments exist to prevent or arrest the progression of myopia. The mechanisms driving refractive development have been localized to the retina, but the retinal pathways and biochemical signaling remain unknown. Based on the assumption that contrast sensitivity and spatial frequency are characteristics of the visual image that drive this response, we hypothesize that the main retinal pathways involved are the ON and OFF pathways. These pathways are proposed to stimulate unique biochemical signals that suppress default excessive eye growth. Thus, normal refractive development relies on constant biochemical feedback derived from retinal pathways activated by normal visual images. We further hypothesize that abnormalities in the visual environment, retinal pathways, or specific biochemical signals will result in down-regulation of the biochemical signaling which then allows for excess eye growth and myopia. In order to test this hypothesis, (Aim 1) the refractive development of specific mouse models with ON or OFF pathway defects will be tested under normal and form deprived visual conditions. In addition, the possibility that ON or OFF pathways originating from rod or cone photoreceptors may control refractive development will be tested by using mice with only functional rods or cones. Refractive development will be assessed by measurements of refractive error and ocular dimensions. The biochemical signals associated with the ON and OFF pathway will be investigated in Aim 2. We hypothesize that dopamine is a putative ON pathway signal. Thus, dopamine synthesis and release will be examined during refractive development in the ON/OFF pathway mutants as well as determining the consequence of the absence of dopamine on refractive development in a retina-specific dopamine deficient mouse. An OFF pathway biochemical signal will be identified using gene profiling in a mouse model with only functional OFF pathways. Candidate genes will then be tested in OFF pathway mutant mice. These experiments are designed to determine the retinal mechanisms of refractive development, thus identifying novel targets for pharmacological or behavioral interventions that could prevent or retard the development of myopia.

出生后眼睛的屈光发育将光功率与轴长相匹配，以聚焦视觉