Multi-Scale Modeling of Vision-Guided Remodeling and Age-Dependent Growth of the Tree Shrew Sclera During Eye Development and Lens-Induced Myopia.

The sclera uses unknown mechanisms to match the eye's axial length to its optics during development, producing eyes with good focus (emmetropia). A myopic eye is too long for its own optics. We propose a multi-scale computational model to simulate eye development based on the assumption that scleral growth is controlled by genetic factors while scleral remodeling is driven by genetic factors and the eye's refractive error. We define growth as a mechanism that changes the tissue volume and mass while remodeling involves internal micro-deformations that are volume-preserving at the macroscale. The model was fitted against longitudinal refractive measurements in tree shrews of different ages and exposed to three different visual conditions: (i) normal development; (ii) negative lens wear to induce myopia; and (iii) recovery from myopia by removing the negative lens. The model was able to replicate the age- and vision-dependent response of the tree shrew experiments. Scleral growth ceased at younger age than scleral remodeling. The remodeling rate decreased as the eye emmetropized but increased at any age when a negative lens was put on. The predictive power of the model was investigated by calculating the susceptibility to scleral remodeling and the response to form deprivation myopia in tree shrews. Both predictions were in good agreement with experimental data that were not used to fit the model. We propose the first model that distinguishes scleral growth from remodeling. The good agreement of our results with experimental data supports the notion that scleral growth and scleral remodeling are two independently controlled mechanisms during eye development.