A New Methodology to Quantify Collagen Remodeling in Glaucoma

Rafael Grytz, PhD
University of Alabama at Birmingham (Birmingham, AL)
Year Awarded:
2015
Grant Duration:
July 1, 2015 to June 30, 2017
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2015115
Award Type:
Standard
Award Region:
US Southern

Recipient of The Thomas R. Lee Award for National Glaucoma Research.

Rafael Grytz, PhD

Quantifying Collagen Remodeling of the Optic Nerve Head

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.

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.

About the Researcher

Rafael Grytz, PhD, is an assistant professor of ophthalmology at the University of Alabama at Birmingham. His area of professional expertise is the study of growth and remodeling mechanisms in living ocular tissues. Dr. Grytz gained extensive interdisciplinary expertise in ocular biomechanics, growth and remodeling mechanisms, and computational mechanics during his PhD training in civil engineering at Ruhr University Bochum in Bochum, Germany and his NIH-funded postdoctoral training in biomedical engineering at the Devers Eye Institute in Portland, Oregon. He has used experimental methods and computational simulation tools to provide insight into biomechanical mechanisms related to glaucoma. For example, Dr. Grytz has provided explanations for the existence of the lamina cribrosa in the human optic nerve head and its remodeling during the development of glaucoma. His research is driven by the desire to elucidate the biomechanical mechanisms that underlie growth and remodeling in ocular conditions and diseases.



"I feel very privileged and grateful to receive this award from BrightFocus Foundation, and I would like to thank the donors. It is very challenging for young investigators with innovative ideas but limited preliminary data to obtain major grant funding. The BrightFocus grant allows me to develop new methodologies and preliminary date to foster a competitive NIH grant application. Your gifts to National Glaucoma Research are critical for fostering new research ideas that can fundamentally change vision health."

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