TY - JOUR
T1 - The immunohistochemical composition of corneal basement membrane in keratoconus
AU - Tuori, Antti J.
AU - Virtanen, Ismo
AU - Aine, Esko
AU - Kalluri, R.
AU - Miner, J. H.
AU - Uusitalo, Hannu M.
N1 - Funding Information:
The skillful technical assistance of Ms. Paula Hasenson, Ms. Marja-Leena Koskinen, Ms. Marja-Leena Piironen and Mr. Reijo Karppinen is kindly acknowledged. We also thank Professor Antti Penttilä for helping us to obtain the normal cornea samples and Mr. Petri Holopainen, Mr. Matti Hyttinen, Mr. Marko Jokinen, Mr. Jouko Kuusela, Mr. Esko Malinen, Mr. Ari Ojamaa, Mr. Taisto Ryyli and Mr. Kari Suomela for collecting the cornea samples at the Department of Forensic Medicine. This study was supported by a project grant from the Faculty of Medicine, University of Helsinki, Finland and by the Finnish Association for Eye Research.
PY - 1997
Y1 - 1997
N2 - 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 β4. 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 α(1/2) (IV) chains, and on the contrary, absence of the expression of some proteins, i.e. collagen α5-6 (IV) chains that normally are continuously expressed in the corneal epithelial BM. In addition, either increased or decreased expression of laminin-1 (α1β1γ1), laminin-5 (α3β3γ2) and collagen type VII, depending on the keratoconus defect, was seen and the expression of integrin β4 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 immunohistochemical 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.
AB - 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 β4. 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 α(1/2) (IV) chains, and on the contrary, absence of the expression of some proteins, i.e. collagen α5-6 (IV) chains that normally are continuously expressed in the corneal epithelial BM. In addition, either increased or decreased expression of laminin-1 (α1β1γ1), laminin-5 (α3β3γ2) and collagen type VII, depending on the keratoconus defect, was seen and the expression of integrin β4 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 immunohistochemical 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.
KW - Collagen type IV
KW - Cornea
KW - Extracellular matrix
KW - Human
KW - Immunohistochemistry
KW - Integrin
KW - Keratoconus
KW - Laminin
UR - http://www.scopus.com/inward/record.url?scp=0030873219&partnerID=8YFLogxK
U2 - 10.1076/ceyr.16.8.792.8989
DO - 10.1076/ceyr.16.8.792.8989
M3 - Article
C2 - 9255508
AN - SCOPUS:0030873219
SN - 0271-3683
VL - 16
SP - 792
EP - 801
JO - Current Eye Research
JF - Current Eye Research
IS - 8
ER -