Genetically testing mechanisms of ocular development and disease

项目摘要 患有眼前段发育不全（ASD）的患者具有发展严重的， 难治性早发性青光眼。50-75%的ASD患者会发展为青光眼， 这发生在比一般人群年轻得多的年龄，导致不成比例的 降低患者及其家属的生活质量。我们认为，内在的血管缺陷是一个主要的 导致ASD损伤与眼周间充质分化缺陷不同。我们将测试 这一假设使用了高度先进的超显微镜，创新的细胞标记方法， 纳米流体技术以及独特和互补的遗传资源。这种病因学上的区别 迁移和分化之间的关系可能对患者分层有重要意义， 预后、可改变风险因素的管理和对潜在危及生命的合并症的认识- 这些都对遗传咨询，计划生育和患者的心理健康非常重要。

PROJECT SUMMARY Patients with ocular anterior segment dysgenesis (ASD) have a greatly elevated risk of developing severe, early onset glaucoma that is refractory to treatment. Between 50-75% of patients with ASD develop glaucoma, which occurs at significantly younger ages than in the general population, leading to disproportionately diminished quality of life for patients and their families. We propose that intrinsic vascular defects are a primary insult contributing to ASD that are distinct from defects in periocular mesenchyme differentiation. We will test this hypothesis using highly advanced ultramicroscopy, innovative cell-labeling approaches, state-of-the-art nanofluidics technologies and unique and complementary genetic resources. This etiological distinction between migration and differentiation may have significant implications for patient stratification with respect to prognosis, management of modifiable risk factors and awareness of potentially life-threatening co-morbidities – all of which are important for genetic counseling, family planning and patients' psychological well being.