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The Underlying Mechanisms of Visual Impairment and Myopia in Prematurity

早产儿视力障碍和近视的潜在机制

基本信息

批准号：
10584723
负责人：
Dao-Qi Zhang
金额：
$ 43.63万
依托单位：
OAKLAND UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-30 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10584723
关键词：
Ablation Amacrine Cells Animal Model Animals Anterior Anterior eyeball segment structure Autopsy Biometry Blindness Blood Vessels Brain Child Contrast Sensitivity Cornea Data Development Dimensions Dopamine Enzymes Event Eye Eye Development Eye diseases Genetic Techniques Goals Growth Human Impairment Infant Interneurons Knock-out Lead Length Light Mediating Molecular Mus Myopia Neurons Outcome Oxygen Oxygen Therapy Care Pathogenesis Pathway interactions Pregnancy Premature Birth Premature Infant Preventive Primates Production Public Health Recovery Refractive Errors Retina Retinal Diseases Retinal Ganglion Cells Retinopathy of Prematurity Signal Pathway Signal Transduction Source System Testing Therapeutic Tyrosine 3-Monooxygenase United States Vascular System Vertebrate Photoreceptors Vision Visual Visual Acuity Visual impairment Work cholinergic combat experience insight lens neonatal mice neuron development novel novel therapeutic intervention patch clamp pharmacologic postnatal premature prenatal preservation rational design response retina blood vessel structure retinal neuron starburst amacrine cell

项目摘要

PROJECT SUMMARY The long-term goal of this project is to determine the neuronal and vascular mechanisms of visual impairment and myopia resulting from prematurity in order to develop preventive and therapeutic strategies. Prenatal and early postnatal vertebrate retinas generate correlated spontaneous neuronal activity, termed “retinal waves,” that are essential for normal neuronal development and vision. Premature retinal wave termination may contribute to preterm birth-associated vision problems and refractive errors. Preterm birth, in combination with postnatal oxy- gen therapy, can also cause retinal vascular complications known as retinopathy of prematurity (ROP). ROP is closely associated with incurable visual impairment and myopia in premature infants. The cellular and molecular mechanisms underlying the pathogeneses of eye disorders related to ROP and the early retinal wave activity termination are not yet well defined. Our objectives in this project are to define how spontaneous retinal waves mediate ocular growth before visual experience and how oxygen-induced retinopathy (OIR) causes vision impairment and myopia. Our preliminary data demonstrated that cholinergic retinal waves generated by starburst amacrine cells (SACs) can excite dopaminergic amacrine cells (DACs), the sole source of ocular dopamine—an ocular development regulator. We hypothesize that cholinergic waves drive normal eye development via dopamine signaling and that suppression of this pathway will disrupt normal ocular growth. In Aim 1, we will test this hypothesis by identifying the cholinergic wave–dopamine signaling pathway and assessing how this pathway impacts ocular growth. In addition, we have found that, in an OIR animal model, AII amacrine cells (AII-ACs) and DACs—two classes of inner retinal neurons that contribute to scotopic and photopic vision, respectively—were substantially lost. We hypothesize that the loss of AII-ACs and DACs in OIR causes myopia. In Aim 2, we will test this hypothesis by determining the relative contributions of AII-ACs and DACs to OIR-induced myopia and assessing the impact of OIR-induced visual impairments on myopia development. Expected outcomes include determining how retinal waves influence dopamine signaling to mediate ocular growth and how oxygen treatment perturbs the rod and cone signaling systems through the loss of retinal interneurons to cause vision loss and the development of myopia. The broader impact of this work on understanding the causes and mechanisms of preterm vision impairment and myopia in children will enable the rational discovery of new therapeutic interventions.

项目总结