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FGF-2 counteracts loss of TGFbeta affected cells from rat lens explants: implications for PCO (after cataract).
- Source :
-
Molecular vision [Mol Vis] 2004 Jul 22; Vol. 10, pp. 521-32. Date of Electronic Publication: 2004 Jul 22. - Publication Year :
- 2004
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Abstract
- Purpose: While cataract surgery initially benefits most patients, many suffer secondary loss of vision because of posterior capsule opacification (PCO). Lens epithelial cells left behind at surgery become aberrant and migrate into the light path. TGF-beta (TGFbeta) appears to play a key role in this process by inducing the cells to undergo an epithelial-mesenchymal transition. Paradoxically, it also typically induces them to undergo apoptotic death. The present study was undertaken to investigate the hypothesis that FGF plays a role in PCO formation by promoting the survival of abnormal cells with PCO-like characteristics.<br />Methods: Rat lens epithelial explants were cultured for one day with TGFbeta2 (25-100 pg/ml) then in control medium with or without FGF-2 (5-100 ng/ml) for up to 31 days, with assessment by light and scanning electron microscopy and immunolocalization.<br />Results: Survival of TGFbeta treated cells was promoted by FGF-2 but not by EGF, PDGF, IGF, or HGF. In the absence of FGF virtually all cells were lost from explants within 5 days. However, when FGF was included cells remained viable throughout culture. These cells, which no longer expressed the lens epithelial marker Pax6, exhibited immunoreactivity for non-lens cell proteins associated with PCO (alpha-smooth muscle actin, type I collagen, and fibronectin) and also beta-crystallin. FGF inclusion also promoted ECM production, multilayering, and plaque formation, features of PCO known to contribute to visual loss.<br />Conclusions: This study points to a key role for FGF in the etiology of PCO and suggests that FGF inhibitors may be useful in preventing PCO.
- Subjects :
- Actins metabolism
Animals
Animals, Newborn
Biomarkers analysis
Cataract metabolism
Cataract pathology
Cell Survival drug effects
Cells, Cultured
Collagen Type I metabolism
Epithelial Cells metabolism
Eye Proteins
Fibronectins metabolism
Fluorescent Antibody Technique, Indirect
Homeodomain Proteins metabolism
Lens Capsule, Crystalline metabolism
Lens, Crystalline metabolism
Microscopy, Electron, Scanning
PAX6 Transcription Factor
Paired Box Transcription Factors
Rats
Rats, Wistar
Repressor Proteins
Transforming Growth Factor beta2
beta-Crystallins metabolism
Cataract etiology
Epithelial Cells cytology
Fibroblast Growth Factor 2 pharmacology
Lens Capsule, Crystalline pathology
Lens, Crystalline cytology
Postoperative Complications
Transforming Growth Factor beta pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 15303087