MyoTreat: Myopia - from genes and environment to cellular responses and treatment

在现代工业社会中，由于近视的发病率和相关并发症的增加，近视已经成为年轻人的一个重要的眼部健康问题，这些问题已经在中年时期造成失明的重大风险。目前的治疗方案效果有限，几年内最大减少约0.4毫米的轴向伸长，相当于近视仅减少约1 d。眼睛的生长受不同生化途径的相互作用控制，一种抑制途径（由视网膜前的成像平面刺激）和一种刺激途径（视网膜后的成像平面）。一种新的未来策略将是激活抑制途径而不是抑制生长刺激途径（大多数研究的标准目标）。目前，对激活生长抑制的干预措施研究甚少。环境因素（环境光的光谱组成）和基因-环境相互作用（特定基因变异及其与关键生活方式暴露的相互作用）对眼睛生长和屈光发育的影响将被研究。新的药理靶点将被确定和测试，并建立生物标志物，以在早期阶段检测近视的发生。我们将研究脉络膜缺氧与脉络膜变薄和眼轴生长的关系，以及它如何与视网膜和巩膜的代谢过程相互作用。将开发新的测量技术，实现人工智能算法，以提高近视研究的诊断，特别是在视野外围。拟议的跨部门和跨学科“MyoTreat”项目（包括解剖学、生理学、药理学、光学和遗传学）将培养近视研究方面的博士生，并产生和传播新的研究成果。最终的科学目标是通过各种动物模型和人类的假设驱动的转化研究，确定近视治疗的新策略。

In modern industrial societies, myopia has become an important ocular health problem of young people, due to its increased incidence and associated complications, which pose a significant risk of blindness already in the middle life span. Current treatment options have limited effects with a maximum reduction of axial elongation by about 0.4 mm over several years, equivalent to a reduction in myopia by only about 1 D. Eye growth is controlled by an interplay of different biochemical pathways, one inhibitory (stimulated by image plane in front of the retina) and one stimulatory (image plane behind the retina). A novel future strategy would be to activate the inhibitory pathways rather than inhibit the growth stimulating pathways (standard target in most studies). At present, interventions to activate growth inhibition are poorly studied. The influence of environmental factors (spectral composition of ambient light) and gene-environment interactions (specific gene variants and their interaction with key lifestyle exposures) on eye growth and refractive development will be investigated. New pharmacological targets will be identified and tested, and biomarkers established to detect the onset of myopia at an earlier stage. It will be studied how choroidal hypoxia relates to choroidal thinning and axial eye growth and how it interacts with the metabolic processes in the retina and sclera. New measurement techniques will be developed that implement artificial intelligence algorithms to improve diagnostics in myopia studies, especially in the periphery of the visual field. The proposed intersectorial and interdisciplinary "MyoTreat" project (including anatomy, physiology, pharmacology, optics, and genetics) will train PhD students in myopia research and generate and disseminate novel research results. The ultimate scientific goal is to identify new strategies for myopia therapy through hypothesis-driven translational research in various animal models as well as in humans.