Upregulation of alphavbeta6 integrin, a potent TGF-beta1 activator, and posterior capsule opacification.
OBJECTIVE
To identify the predominant activation pathway of transforming growth factor (TGF)-beta1 in the lens capsule, studying the spatial and temporal expression pattern of alphavbeta6 and thrombospondin-1. Other PCO-related proteins were also studied.


METHODS
Departments of Ophthalmology and Optometrics and Clinical Pathology, Medical School, University of Vienna, Vienna, Austria.


METHODS
The lens capsules of 12 human donor eyes were cultivated in a protein-free medium for up to 28 days (cultivated lens capsules [CLCs]) after lens extraction. Ten intact lenses (ILs) served as the control group and were also cultured. During the culture period, cell dynamics were observed by phase-contrast microscopy. Proteins were detected by double immunofluorescence on frozen sections.


RESULTS
In ILs, alphavbeta6 was absent but 91.6% of the CLCs showed extensive staining. Remnant lens epithelial cells (LECs) expressed alphavbeta6 immediately after lens extraction. The alphavbeta6 was detected throughout the culture period in all regions of the capsule. Thrombospondin-1 was absent in ILs and CLCs, suggesting that this protein is not significant in TGF-beta1 activation in the lens. Transforming growth factor-beta1 was abundantly expressed in all ILs and CLCs, slightly decreasing during intensive LEC proliferation and migration. The TGF-beta receptor II (RII) was expressed equally in all specimens, decreasing with culture time. Nonresident extracellular matrix proteins and alpha-smooth muscle actin were partially detected in CLCs but not in ILs. Latent TGF-beta binding protein 1 and collagen III were absent in all specimens. All cells found in the cultures expressed vimentin and alphaB-crystallin (LEC markers).


CONCLUSIONS
Alphavbeta6 is the main activator of TGF-beta1 in the lens capsule and represents a new target for PCO prevention.
Sponer
Ulrike
U
Department of Ophthalmology and Optometrics, General Hospital, University of Vienna, Austria.
Pieh
Stefan
S
Soleiman
Afschin
A
Skorpik
Christian
C
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002386:Cataract / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007903:Lens Capsule, Crystalline / Q000378:metabolism* / Q000473:pathology; D007908:Lens, Crystalline / Q000378:metabolism; D008875:Middle Aged; D009924:Organ Culture Techniques; D011183:Postoperative Complications / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D000199:Actins; D000951:Antigens, Neoplasm; D016326:Extracellular Matrix Proteins; D016023:Integrins; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C073878:integrin alphavbeta6; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II