Myopia is a global health concern, with projected estimates that nearly half of the world\u27s population will be myopic by 2050. While its refractive aspect can be corrected, the heightened susceptibility to sight-threatening comorbidities, particularly with high myopia, remains a challenge. Among these comorbidities, glaucoma is a major concern, with myopia recognized as an independent risk factor. However, the mechanistic link between myopia and glaucoma remains poorly understood. This dissertation investigates the multiscale remodeling changes in experimental high myopia and their potential implications for increased risk of glaucoma later in life. Using a multimodal approach, this dissertation investigates: (1) neural canal opening remodeling and thickness changes of peripapillary tissues during juvenile high myopia development, (2) the impact of sustained high myopia on peripapillary tissues from juvenile age until early adulthood, and (3) changes in retinal function, optic nerve axonal counts, and retinal proteomics during juvenile high myopia development. The findings of these studies revealed that juvenile experimental high myopia induces progressive asymmetric deformations of the neural canal opening and heterogeneous thinning of peripapillary tissues, where the retina was relatively protected. Furthermore, sustained negative lens wear into early adulthood induced progressive myopia in a subset of eyes, where profound choroidal thinning during early myopia development emerged as a potential biomarker for future chorioscleral thinning and myopia progression. Lastly, while retinal function and optic nerve axonal counts were preserved during the juvenile stage of myopia, retinal proteomics identified differential modulation of key molecular pathways that may serve to protect the retina against various myopia-induced insults. These findings advance our understanding of the myopia remodeling changes and may suggest mechanistic links between myopia and glaucoma. The observed asymmetric remodeling of the neural canal opening and peripapillary tissues may alter the biomechanical environment at the ONH, potentially increasing the risk of pathological ONH remodeling and subsequent glaucoma development later in life. Moreover, the identified retinal protective mechanisms may become exhausted with aging, thereby heightening susceptibility to neurodegenerative conditions such as glaucoma. Lastly, this work identifies a potential biomarker for predicting progressive myopia, thereby offering novel avenues for early intervention and targeted therapeutic strategies
