Vitreous-induced modulation of integrins in retinal pigment epithelial cells: effects of fibroblast growth factor-2.

Growth in the presence of vitreous results in transformation of human RPE cells from an epithelioid to a fibroblast-like appearance and leads to an elevation of the expression of alpha(5) and alpha(2) integrins, while the level of alpha(3) integrin is reduced. These changes are inhibited by the presence of FGF-2. Vitreous treatment increases mobility, as does antibody neutralization of FGF-2 or antibody blockade of FGF receptors. The vitreous-induced rise in mobility depends on an increase in alpha(5) integrin expression since it is inhibited by anti-alpha(5) integrin antibodies. Expression of alpha(5) integrin as a result of infection of RPE cells with an alpha(5) integrin-encoding adenovirus induced morphological transformation and an increase in mobility similar to that seen with vitreous. It is concluded that a decrease in FGF-2 plays an important role in vitreous-induced alterations of RPE cell morphology, integrin expression and mobility. High FGF-2 levels prevent at least some of the increased mobility of RPE cells induced by vitreous. This is mediated via extracellular FGF-2 binding to FGF receptor(s) since antibodies to FGF-2 or to its receptor(s) mimic the effects of vitreous. Changes in mobility and morphology involve altered alpha(5) integrin expression since mobility is blocked by antibodies against these proteins while elevated alpha(5) integrin expression increases mobility and leads to morphological changes.

Little effect of tissue plasminogen activator in subretinal surgery for acute hemorrhage in age-related macular degeneration.

We studied the effect of intraoperative fibrinolysis prior to surgical evacuation of subretinal hemorrhage, which has been recommended as a valuable adjunct in the surgical treatment of submacular hemorrhage. We analyzed retrospectively the records of eight patients who underwent pars plana vitrectomy combined with subretinal injection of tissue plasminogen activator (TPA). The duration of symptoms ranged from 2 h to 14 days (median 1.5 days). During vitrectomy, TPA (6-75 micrograms) was injected subretinally through a retinotomy. After 20 min the liquified blood was surgically drained. The residual clot had to be extracted mechanically through an enlarged retinotomy site. In all patients, fibrinolysis was incomplete and an additional mechanical clot extraction was necessary. The postoperative visual acuity improved slightly in four patients, stabilized at the preoperative level in three patients, and worsened in one patient. During follow-up, one patient suffered from retinal detachment. In four patients a cataract developed. In all eyes, large defects of the retinal pigment epithelium resulted. In contrast to other authors, we did not find an acceptable liquefaction of the subretinal clot that would have facilitated surgical extraction of the hemorrhage. Therefore, a therapeutic benefit from the injection of TPA before removal of a subretinal hemorrhage was not distinct.

Functions of estrogens and anti-estrogens in the rat endometrial adenocarcinoma cell lines RUCA-I and RUCA-II.

Inbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone-dependent endometrial adenocarcinoma. Here we characterize the RUCA-I cell line derived from an endometrial adenocarcinoma of an inbred DA/Han rat and the RUCA-II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA-I cell line, if transplanted to the neck of female DA/Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub-class. In contrast, ectopic tumor growth of the RUCA-II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA-I and RUCA-II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA-binding state. In contrast, the rate of proliferation of RUCA-I but not of RUCA-II cells was reduced in the presence of 10(-6) M tamoxifen. From these results we conclude that (i) both cell lines, RUCA-I and RUCA-II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone-dependent growth regulation of RUCA-I and RUCA-II cells is obviously impaired; (iii) the RUCA-I cell line appears to be a suitable model system for the study of molecular aspects of estrogen- and tamoxifen-dependent gene expression.