Classifications of vitreomacular traction syndrome: diameter vs morphology.

PURPOSE: The aim of this study is to analyze the agreement between the classifications based on morphology and diameter of vitreomacular traction (VMT) syndrome, as well as to correlate the morphological findings of VMT with specific maculopathies. METHODS: Fifty-three eyes with VMT syndrome were categorized into two classifications based on optical coherence tomography images: the VMT morphology (V- or J-shaped) and the diameter of adhesion (focal ≤ 1500 µm or broad>1500 µm). RESULTS: High correlation was seen between V-shaped and focal-VMT and between J-shaped and broad-VMT (kappa=0.850; P<0.001), except in four cases with broad adhesion despite the presence of a V-shaped pattern. These four cases had common characteristics to those with broad vitreal attachment regarding associated maculopathies and visual function. V-shaped VMT (n=29) and focal-VMT (n=25) led to tractional cystoid macular edema (CME; 79.31% and 84%, respectively) and macular hole (MH; 37.93% and 44%); J-shaped VMT (n=24) and broad-VMT (n=28) were associated with epiretinal membranes (ERMs; 91.66% and 92.85%, respectively) and diffuse retinal thickening (62.50% and 64.28%). The best-corrected visual acuity (BCVA) was not significantly different between the groups (BCVA logarithm of the minimum angle of resolution: V-shaped, 0.45; J-shaped, 0.46; P=0.816; and focal, 0.50; broad, 0.42; P=0.198). CONCLUSIONS: Although highly concordant, the classification based on the diameter of the adhesion and not on the classical adhesion morphology seemed to better reflect the specific macular changes. V-shaped and focal VMT led to tractional CME and MH, while J-shaped and broad VMT were associated with ERM and diffuse retinal thickening.

Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors.

Transforming growth factor beta (TGFbeta), the most established promoter of myofibroblast differentiation, induces ED-A cellular fibronectin and alpha-smooth muscle actin expression in fibroblastic cells in vivo and in vitro. ED-A fibronectin exerts a permissive action for alpha-smooth muscle actin expression. A morphological continuity (called fibronexus), a specialized form of focal adhesion, has been described between actin stress fibers that contain alpha-smooth muscle actin, and extracellular fibronectin, which contains the ED-A portion, in both cultured fibroblasts and granulation tissue myofibroblasts. We have studied the development of these focal adhesions in TGFbeta-treated fibroblasts using confocal laser scanning microscopy, three-dimensional image reconstruction and western blots using antibodies against focal adhesion proteins. The increase in ED-A fibronectin expression induced by TGFbeta was accompanied by bundling of ED-A fibronectin fibers and their association with the terminal portion of alpha-smooth muscle actin-positive stress fibers. In parallel, the focal adhesion size was importantly increased, and tensin and FAK were neoexpressed in focal adhesions; moreover, vinculin and paxillin were recruited from the cytoplasmic pool into focal adhesions. We have evaluated morphometrically the length and area of focal adhesions. In addition, we have evaluated biochemically their content of associated proteins and of alpha-smooth muscle actin after TGFbeta stimulation and on this basis suggest a new focal adhesion classification, that is, immature, mature and supermature. When TGFbeta-induced alpha-smooth muscle actin expression was blocked by soluble recombinant ED-A fibronectin, we observed that the fragment was localised into the fibronectin network at the level of focal adhesions and that focal adhesion supermaturation was inhibited. The same effect was also exerted by the ED-A fibronectin antibody IST-9. In addition, the antagonists of actin-myosin contractility BDM and ML-7 provoked the dispersion of focal adhesions and the decrease of alpha-smooth muscle actin content in stress fibers of pulmonary fibroblasts, which constitutively show large focal adhesions and numerous stress fibers that contain alpha-smooth muscle actin. These inhibitors also decreased the incorporation of recombinant ED-A into fibronectin network. Our data indicate that a three-dimensional transcellular structure containing both ED-A fibronectin and alpha-smooth muscle actin plays an important role in the establishment and modulation of the myofibroblastic phenotype. The organisation of this structure is regulated by intracellularly and extracellularly originated forces.