Increased Levels of Serum Fibroblast Growth Factor-2 in Diabetic Pregnant Women with Retinopathy1

What is it about?

FIBROBLAST GROWTH factor-2 (FGF-2) is a potent mitogen and angiogenic factor widely expressed in the embryo and fetus (1). It is normally absent from the circulation in adult life, but is found in patients with a variety of neoplasias and with degenerative diseases such as Duchenne muscular dystrophy (2–5). Immunoreactive FGF-2 is also present in the human fetal circulation from at least the early second trimester and appears in maternal blood during normal pregnancy (6). Immunoreactive FGF-2 rapidly disappears from the maternal circulation postpartum, suggesting that it may be derived from the placenta or fetal membranes (6–8). Maternal circulating FGF-2 is associated with a binding protein identified by us as a truncated form of the FGF receptor-1 (FGFR1). The amounts of immunoreactive FGF-2 found in term pregnant woman are substantially elevated in pregnancies complicated by type 1 or gestational diabetes (9). A major complication of poorly controlled diabetic pregnancy is proliferative retinopathy. The angiogenic actions of FGF-2 both in vitro and in vivo (1) have prompted others to examine its presence in diabetic proliferative retinopathy outside of pregnancy. Both immunoreactive FGF-1 (acidic FGF) and FGF-2 (basic FGF) have been identified in preretinal membranes from patients with diabetic retinopathy and proliferative vitreoretinopathy and in the vitreous humor (10 –14). Levels of FGF-2 were greatest in vitreous humor from patients with proliferative diabetic retinopathy in whom neovascularization of the disk or iris was evident (13). Such findings have implicated locally produced FGFs in the etiology of diabetic retinopathy. However, as pregnancy is normally associated with a circulating component of FGF-2, we have examined here whether this may differ between pregnant patients with type 1 diabetes with or without angiogenic eye disease.

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Why is it important?

The amount of FGF-2 found in serum during the early second trimester in diabetic patients with retinopathy would be sufficient to cause endothelial cell proliferation in vitro. Whether the circulating FGF-2 is causally related to retinopathy in diabetic pregnancy is unknown, but evidence exists to suggest that this is possible. Immunoreactive FGF-2 is present in the vitreous humor of diabetic patients and in preretinal membranes, and is greatest in patients with proliferative disease (11, 13, 15). FGF-BPs representing truncated FGFR1 receptor have also been identified in vitreous humor (29). Given the proven angiogenic capacity of FGF-2 in the eye in animal models, it seems likely that a local production of FGF-2 could contribute to proliferative retinopathy. In diabetic pregnancy, locally produced FGF-2 may be supplemented by that derived from the circulation, although the pharmacokinetics in relation to circulating FGF-BP are not known

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