The immunohistochemical composition of corneal basement membrane in keratoconus

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Abstract
PURPOSE. Keratoconus is a gradually progressing disease of unknown cause, characterized by central thinning, increased curvature, and finally scarring of the cornea. This causes myopia and astigmatism and the ultimate treatment is keratoplasty. We studied the composition of basement membranes (BMs) in normal, scarred and keratoconus corneas to find out possible changes specific for keratoconus. METHODS. Frozen sections of normal, scarred and keratoconus corneas were immunostained with various antibodies against basement membrane (BM) proteins and integrin ß 4. RESULTS. In the keratoconus corneas, we found discontinuities or defects in Bowman's layer, sometimes distorted stroma beneath the defects, and also thinning of the stroma. The results show that within the defects in keratoconus corneas, there is an expression of proteins that are not normally present in the corneal BM, i.e. collagen a 1/2 (IV) chains, and on the contrary, absence of the expression of some proteins, i.e. collagen a 5-6 (IV) chains that normally are continuously expressed in the corneal epithelial BM. In addition, either increased or decreased expression of laminin-1 (a1ß1?1), laminin-5 (a3ß3?2) and collagen type VII, depending on the keratoconus defect, was seen and the expression of integrin b4 was decreased. These findings seem to be specific for keratoconus, as they were not found in scarred corneas. CONCLUSIONS. The results show that the defects in BM and changes in the BM composition are involved in the pathogenesis of keratoconus. Furthermore, it seems that scarring alone does not explain the breaks in Bowman's layer and immuno-histochemical changes seen in keratoconus. Therefore, we suggest that a process similar to wound healing, which is initiated by breaks in Bowman's layer, would largely contribute to the differences seen in keratoconus corneas.