What part does the white of the eye play in glaucoma?
Research details
- Type of funding: Project Grant
- Grant Holder: Dr Craig Boote
- Institute: Cardiff University
- Region: Wales
- Start date: January 2012
- End Date: February 2015
- Priority:
- Eye Category:
Overview
Glaucoma is one of the leading causes of sight loss in the UK. It’s often linked to high pressure in the eye, which can squeeze and damage the cells that form the optic nerve (retinal ganglion cells). This can lead to permanent sight loss.
The main site of damage in glaucoma is at the optic nerve head, where 1-2 million retinal ganglion cell connections come together. And the potential damage that high eye pressure can cause is transmitted to the optic nerve head via the white of the eye (the sclera).
So in this project, the research team was trying to find out more about how the sclera behaves under high eye pressure conditions. They used high-power x-ray and microscope technology to study the way collagen is arranged within the sclera. (Collagen is one of two types of protein that make up the sclera.)
The team used their detailed observations to build computer models that predict the mechanics of how the sclera responds to high pressure in the eye.
High eye pressure rearranges collagen
Their results show that as eye pressure rises, collagen in the sclera rearranges in a way that could make optic nerve damage more likely. This is really interesting because it could open up a whole new approach to developing treatment for glaucoma.
At the moment the main treatment for glaucoma due to high eye pressure is by trying to lower the pressure. But this doesn’t work for everyone.
This study shows that it might be possible to halt sight loss by changing the mechanics of the sclera instead, for example by ‘collagen cross-linking’. This is a treatment that’s used in keratoconus to make the front surface of the eye (the cornea) stronger.
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Scientific summary
The role of the sclera in human glaucoma
Elevated intraocular pressure (IOP) is a major glaucoma risk factor. However the exact role IOP plays in the retinal ganglion 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 (ONH) initiates a cascade of events that ultimately result in axonal dysfunction and apoptosis. The physical effects of IOP on nerve head axons are primarily mediated through the response of the sclera, the eye’s main supporting tissue. The sclera’s response to IOP is, in turn, dependent upon a fibrous network of collagen and elastin that constitutes the bulk of the scleral extracellular matrix. Accurate characterisation of scleral fibre architecture is therefore vital in order to understand and model the tissue’s physiological behaviour, and hence its role in glaucoma. However, despite its clinical importance, the precise arrangement of scleral collagen/elastin remains unknown.
This project employs a powerful new synchrotron x-ray scattering method, alongside complimentary electron and multiphoton microscopy imaging tools, to quantify the detailed collagen/elastin fibre architecture of glaucomatous and non-glaucomatous posterior human scleras. The information is being used as a platform to build finite-element models to accurately describe scleral behaviour under normal/elevated IOP, and thereby its projected influence on nerve head axons. Models are being refined against data from in-vitro scleral inflation methods which simulate the eye’s physiological loading conditions, in order to establish new injury risk factors which will drive the development of scleral-targeted therapies.
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Publications
- Coudrillier B, Pijanka JK, Jefferys JL, Goel A, Quigley HA, Boote C, et al. Glaucoma-related Changes in the Mechanical Properties and Collagen Micro-architecture of the Human Sclera. PLoS ONE [Internet]. 2015 Jul 10 [cited 2015 Oct 1];10(7):e0131396.
- Coudrillier B, Pijanka J, Jefferys J, Sorensen T, Quigley HA, Boote C, et al. Effects of age and diabetes on scleral stiffness. J Biomech Eng. 2015 Jul;137(7).
- Pijanka JK, Spang MT, Sorensen T, Liu J, Nguyen TD, Quigley HA, et al. Depth-Dependent Changes in Collagen Organization in the Human Peripapillary Sclera. PLoS One [Internet]. 2015 Feb 25 [cited 2015 Oct 1];10(2).
- Coudrillier B, Pijanka J, Jefferys J, Sorensen T, Quigley HA, Boote C, et al. Collagen structure and mechanical properties of the human sclera: analysis for the effects of age. J Biomech Eng. 2015 Apr;137(4):041006.
- Pijanka JK, Kimball EC, Pease ME, Abass A, Sorensen T, Nguyen TD, et al. Changes in Scleral Collagen Organization in Murine Chronic Experimental Glaucoma. Invest Ophthalmol Vis Sci [Internet]. 2014 Oct [cited 2015 Oct 1];55(10):6554–64.
- Pijanka JK, Abass A, Sorensen T, Elsheikh A, Boote C. A wide-angle X-ray fibre diffraction method for quantifying collagen orientation across large tissue areas: application to the human eyeball coat. Journal of Applied Crystallography [Internet]. 2013 Oct 1 [cited 2015 Oct 1];46(5):1481–9.
- Coudrillier B, Boote C, Quigley HA, Nguyen TD. Scleral anisotropy and its effects on the mechanical response of the optic nerve head. Biomech Model Mechanobiol. 2013 Oct;12(5):941–63.
- Pijanka JK, Coudrillier B, Ziegler K, Sorensen T, Meek KM, Nguyen TD, et al. Quantitative mapping of collagen fiber orientation in non-glaucoma and glaucoma posterior human sclerae. Invest Ophthalmol Vis Sci. 2012 Aug;53(9):5258–70.
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Meet the team
Dr Craig BooteDr Craig Boote is a senior lecturer at Cardiff University. In his research he uses high-powered x-ray imaging techniques to study the structure and mechanics of the cornea and sclera.
You can listen to him talking about his research on the RNIB's Insight Radio, together with Fight for Sight's Director of Research, Dr Dolores M Conroy.
