Summary

Glaucoma is a leading cause of blindness and the progressive remodeling and excavation of the connective tissues of the optic nerve head is a common feature of all glaucoma phenotypes, yet little is known about the underlying mechanisms. To study growth and remodeling mechanisms in glaucoma is very challenging, as the underlying mechanisms occur at very different length scales (from an elevated intraocular pressure (IOP) at the organ level to a potential alteration of the collagen fibril structure at the micro-scale). Also, because it is surrounded by other tissues, the optic nerve head, the site of initial axonal damage in glaucoma, is not directly accessible for imaging. We propose to develop a novel imagining and quantification methodology, and to use this methodology together with a new animal model to gain insight into the growth and remodeling mechanisms that underlie glaucoma.

Project Details

The goal of this project is to develop a novel imagining and quantification methodology, and to use this methodology together with a new animal model to gain insight into the growth and remodeling mechanisms that underlie glaucoma.

In our first aim, we propose to develop a multi-scale imaging methodology to quantify biomechanical and microstructural properties of the optic nerve head. We will use a novel fluorescent probe and two-photon microscopy to the study the microstructure of the optic nerve head at different IOP levels. In the second aim, we will apply our new imaging methodology to study the biomechanical and microstructural changes of the optic nerve head after chronic IOP elevation.

At present, the biomechanical properties of the optic nerve head, and how these properties change in glaucoma due to growth and remodeling, are mostly unknown. The innovative aspect of this proposal is twofold: first, the development of a novel imaging and quantification methodology based on multiphoton florescence microscopy; and second, the use of the tree shrew as a new animal model to elucidate multi-scale growth and remodeling mechanisms in glaucoma.

The role of IOP in ocular diseases remains controversial due to the wide spectrum of individual susceptibility to IOP and IOP-driven growth and remodeling. Once our study is complete, the proposed methodology we have developed may not only provide insight into the role of growth and remodeling mechanisms in glaucoma, but also provide an experimental platform for the development of novel treatment modalities based on altering collagen remodeling in the optic nerve head.