TGF-beta1, TGF-beta receptor II and ED-A fibronectin expression in myofibroblast of vitreoretinopathy.
OBJECTIVE
Formation of scarlike epiretinal membranes (ERMs) constitutes potentially the end stage of evolution of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Among various cellular populations, ERMs contain cells with contractile features typical of myofibroblasts. The current study was conducted to investigate the presence of transforming growth factor (TGF)-beta1, TGF-beta receptor II (RII) and ED-A fibronectin (FN), the main inducers of myofibroblastic differentiation in ERMs in PDR and PVR.


METHODS
Samples of ERM were obtained from 23 patients during microsurgery for PVR or PDR. Electron microscopy, immunohistochemistry, and confocal microscopy with antibodies recognizing beta-smooth muscle (SM) actin, desmin, TGF-beta1, TGF-beta receptors I and II, and ED-A FN were performed.


RESULTS
alpha-SM actin was detected in all ERMs, whereas desmin was present in 50% of the cases. ED-A FN was expressed in all ERMs in close relation with alpha-SM actin-positive myofibroblasts. In addition, TGF-beta1 and TGF-beta R II were always present, TGF-beta RII being expressed in both alpha-SM actin-positive and negative fibroblastic cells.


CONCLUSIONS
Myofibroblast accumulation is a key event in ERM-associated traction retinal detachment occurring during PVR and PDR. The current results suggest that the presence of alpha-SM actin-positive myofibroblasts is probably dependent on the concomitant neoexpression of TGF-beta1, TGF-beta RII, and ED-A FN. The results furnish new data on the mechanism of alpha-SM actin stimulation in fibroblasts in a human pathologic setting.
Bochaton-Piallat
M L
ML
Department of Pathology, University of Geneva, Switzerland.
Kapetanios
A D
AD
Donati
G
G
Redard
M
M
Gabbiani
G
G
Pournaras
C J
CJ
D000199:Actins / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology; D019773:Epiretinal Membrane / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005353:Fibronectins / Q000096:biosynthesis*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology
D000199:Actins; D005353:Fibronectins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II