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

在现代工业社会中，近视已经成为年轻人的重要眼部健康问题，这是由于其增加的发病率和相关并发症，其在中年期已经造成失明的显著风险。目前的治疗方案效果有限，几年内最大轴向伸长减少约0.4 mm，相当于近视减少仅约1 D。眼睛生长是由不同的生物化学途径的相互作用控制的，一种是抑制性的（由视网膜前面的图像平面刺激），另一种是刺激性的（视网膜后面的图像平面）。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（大多数研究中的标准目标）。目前，激活生长抑制的干预措施研究得很少。将研究环境因素（环境光的光谱组成）和基因-环境相互作用（特定基因变体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。将确定和测试新的药理学靶点，并建立生物标志物以在早期阶段检测近视的发病。将研究脉络膜缺氧如何与脉络膜变薄和眼轴生长相关，以及它如何与视网膜和巩膜中的代谢过程相互作用。将开发新的测量技术，实施人工智能算法，以改善近视研究中的诊断，特别是在视野周边。拟议的跨部门和跨学科的“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在各种动物模型和人类中进行假设驱动的转化研究来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.