Dr Craig Boote
Research Topics and Related Projects:
Fig. 1: SHG multiphoton microscopy images showing collagen fibril bundles as a function of tissue depth in the posterior sclera of a human eye
The role of scleral and optic nerve head micro-architecture in glaucoma.
Elevated IOP is a major glaucoma risk factor. However the exact role that IOP plays in the RGC cell loss that characterises glaucoma is unknown. The biomechanical model of glaucoma proposes that IOP-induced deformation in and around the lamina cribrosa of the optic nerve head results in axonal dysfunction and apoptosis. The physical effects of IOP on nerve head axons are primarily mediated by the collagen-rich tissues of the lamina cribrosa and surrounding sclera. Our research aims are to: (i) characterise scleral and laminar tissue micro-architecture as a function of age and glaucoma, and (ii) use this information to determine the biomechanical factors that underpin glaucoma susceptibility and pathogenesis. We have developed novel synchrotron x-ray scattering and laser scanning multiphoton imaging (Fig. 1) tools, to quantify scleral and laminar collagen fibre arrangement, and are using the information to build finite-element models to describe the mechanical behaviour of these tissues under normal/elevated IOP, and thereby their projected influence on nerve head axons.
Corneal dysfunction and the development of therapeutic strategies.
The cornea is a uniquely transparent, precisely curved tissue whose functionality depends heavily on the hierarchical structure and complex micro-anatomy of its extracellular matrix. Despite their importance for vision, the fundamental basis of corneal transparency and shape, and their compromise due to injury and disease, is not fully understood. Our ultimate objective is to relate loss of transparency and changes in corneal shape/astigmatism to tissue micro- and ultra-structure. We are using x-ray scattering methods (Fig. 2) and a range of complementary microscopic imaging modalities to determine in three-dimensions the relationships between the constituent collagen, proteoglycans and cells within normal and pathological mature/developing corneas, post-surgical corneas and emerging biosynthetic corneal replacements. Our aims are to: (i) model corneal transparency at the cellular and fibrillar level, and use this to explain the loss of transparency in a range of pathological conditions, including corneal wounds; (ii) characterize the full three-dimensional structure of the cornea, explain the structural basis of astigmatism, and demonstrate how ectatic and astigmatic pathologies and their surgical treatments can be modelled and their effect on the cornea’s macroscopic behaviour predicted by finite element analysis; (iii) develop methodologies for stabilizing corneal curvature and restoring transparency, including cell-based and photochemical cross-linking methods.
Fig. 2: Collagen fibril orientations in the human cornea, as determined using wide-angle x-ray scattering
Boote C (PI) & Meek KM, £122,672, Project Grant: "The role of the sclera in human glaucoma", Fight For Sight, 2012-2014.
Meek KM (PI), Quantock AJ, Knupp C, Boote C, £1.75M, Programme Grant: "The ultrastructural basis of corneal dysfunction and the development and optimization of novel therapeutic strategies", MRC, 2012 - 2017.
Dr Jacek Pijanka, Research Associate, "The role of the sclera in human glaucoma", Fight For Sight, 2012-2014.
Dr Harry Quigley, Wilmer Ophthalmological Institute, Johns Hopkins University.
Prof. Thao Nguyen, Department of Mechanical Engineering, Johns Hopkins University.
Prof. Ahmed Elsheikh, School of Engineering, University of Liverpool.
Prof. Rafael Grytz, Department of Ophthalmology, University of Alabama.