Structural organisation of collagen in the corneas of primates and other mammals and the stromal changes associated with the disease keratoconus
X-ray diffraction was used to determine the ultrastructural arrangement of collagen in the normal human, monkey and bovine cornea. Using the same technique, the ultrastructural organisation of collagen in human keratoconus corneal buttons and in the corneas of mice with a murine specific keratopathy (SKC), in which the males develop a cone shaped cornea, was also examined. Collagen fibrils were found to be most closely packed in the prepupillary region of the normal human cornea, suggesting an optimisation of tissue strength and transparency in the main optical zone. In humans and marmoset monkeys, fibril size and interfibrillar spacing increased rapidly at the limbus to provide additional tensile strength at the point where the cornea meets the less curved sclera. A difference in the preferred orientation of collagen fibrils was observed between human and bovine corneas. Throughout the human corneal stroma, (and predominantly in the posterior stroma), collagen fibrils are preferentially aligned in the superior-inferior and nasal-temporal directions this alignment coincides with the insertion points of the rectus muscles. The proportion of aligned collagen mass (relative to the total collagen mass), which increases in all four quadrants of the peripheral human cornea, is highest in the superior-nasal and inferior-temporal regions, revealing a symmetry between the left and right cornea in terms of collagen mass distribution. Abnormalities in collagen orientation and mass distribution were seen in the majority of keratoconus corneal buttons examined. A relationship between the size and shape of the cone and the extent of the structural alterations was seen in some cases however a large variation existed between corneas. These results are consistent with a theoretical mechanism of keratoconus progression which involves enzyme action and inter-fibrillar and inter-lamellar slippage. Examination of the structural organisation of collagen in SKC mice corneas, revealed the strain to be an unsuitable model for studying human keratoconus.