Alpha11 integrin in the human cornea: importance in development and disease.
OBJECTIVE
To examine the distribution of the alpha11 integrin chain in the human cornea during fetal development and in normal and diseased adult human corneas.


METHODS
Six fetal corneas, 10 to 20 weeks of gestation (wg), and 18 adult corneas including 3 normal, 7 with keratoconus, 5 with pseudophakic bullous keratopathy (PBK), 2 with Fuchs' corneal dystrophy, and 1 with a scar after deep lamellar keratoplasty (DLKP) were processed for immunohistochemistry with specific antibodies against the alpha11 integrin chain; collagen I, IV, and V; and alpha-smooth muscle actin (alpha-SMA). The cellular source of alpha11 integrin chain was further investigated in cell cultures.


RESULTS
At 10 to 17 wg, the alpha11 integrin chain was predominantly present in the anterior corneal stroma. At 20 wg, in normal adult corneas and in Fuchs' dystrophy corneas there was weak staining in the stroma. The PBK corneas showed variable and weak staining, generally accentuated in the posterior stroma near Descemet's membrane. In contrast, the anterior portion of the stroma in the keratoconus corneas was strongly stained in an irregular streaky pattern. Human corneal fibroblasts/myofibroblasts produced alpha11 integrin chain in culture. Cultures treated with TGF-beta showed higher content of both alpha-SMA and the alpha11 integrin chain.


CONCLUSIONS
The presence of the alpha11 integrin chain during early corneal development and the enhanced expression in scarred keratoconus corneas indicates that this integrin chain is likely to play an important role in collagen deposition during corneal development and in keratoconus with a scarring component and compromised basement membrane integrity.
Byström
Berit
B
Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå, Sweden.
Carracedo
Sergio
S
Behndig
Anders
A
Gullberg
Donald
D
Pedrosa-Domellöf
Fatima
F
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D024062:Collagen Type V / Q000378:metabolism; D003315:Cornea / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003316:Corneal Diseases / Q000378:metabolism* / Q000601:surgery; D016039:Corneal Transplantation; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005865:Gestational Age; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009132:Muscles / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055815:Young Adult
C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D024141:Collagen Type IV; D024062:Collagen Type V; C121535:ITGA11 protein, human; D039001:Integrin alpha Chains; D016212:Transforming Growth Factor beta