FGF-2 counteracts loss of TGFbeta affected cells from rat lens explants: implications for PCO (after cataract).
OBJECTIVE
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.


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.


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.


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.
Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, New South Wales, Australia.
Kylie J
KJ
Mansfield
Anna
A
Cerra
Coral G
CG
Chamberlain
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D002386:Cataract / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018398:Homeodomain Proteins / Q000378:metabolism; D007903:Lens Capsule, Crystalline / Q000378:metabolism / Q000473:pathology*; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2; D038204:beta-Crystallins / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D024042:Collagen Type I; D005136:Eye Proteins; D005353:Fibronectins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D038204:beta-Crystallins; D016222:Fibroblast Growth Factor 2