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B. P. Palka, H. Tanioka, C. Sotozono, N. Yagi, C. Boote, R. D. Young, K. M. Meek, S. Kinoshita, A. J. Quantock; Reduced Collagen Interfibrillar Spacing in Macular Corneal Dystrophy Occurs Predominantly in Deep Stromal Layers. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3926. doi: https://doi.org/.
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In macular corneal dystrophy (MCD) the centre-to-centre collagen fibril spacing is reduced by over 20%, when taken as an average throughout the whole depth of the stroma (Quantock et al., Curr Eye Res 1990;9:393-398). To investigate whether this occurs uniformly across the stroma or is more prevalent at certain stromal depths we undertook a depth-profiled study of collagen interfibillar spacing in MCD.
The left cornea of a 50-yr-old womanwith MCD was obtained at keratoplasty. Tissue was immediately wrapped in Clingfilm to prevent dehydration and stored at -80°C for 7days prior to transportation on dry ice to the SPring-8 synchrotron. Two thin strips of tissue, approximately 400 microns wide, were dissected across the central cornea. One strip was analysed with the X-ray beam directed through the corneal strip from front to back, whilst the second strip was oriented so that the beam passed through the corneal strip edgeways. On the high flux beamline 40XU, a series of small-angle X-ray diffraction patterns were obtained with a 25µm microbeam in 25µm steps. Patterns were analyzed to provide values for the mean collagen interfibrillar Bragg spacing. Dissected strips from an eye-bank cornea were similarly examined.
Collagen interfibrillar Bragg spacing in the MCD cornea, as an average across the whole thickness of the stroma, was 24.6% lower than in the eye bank cornea (p<0.001). In the eye bank cornea collagen fibril spacing was approximately 25% lower in the anterior stroma than in the mid-depth or deep stroma, in line with the findings of a previous study (Quantock et al., J Appl Crystal 2007;40:335-340). The situation was reversed in the MCD cornea, however, with collagen fibril spacing dropping linearly with depth from the anterior to posterior cornea, being some 7-10% lower in the posterior 100µm of the MCD stroma compared to the anteriormost 100µm (p<0.001).
Collagen fibril spacing is reduced in MCD, preferentially so in deeper stromal regions. A defect in proteoglycan metabolism underlies MCD, and we speculate that the proportionally larger reduction in collagen fibril spacing in the deep stroma is a consequence of the differential proteoglycan population throughout the corneal depth.
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