Growth factors and their receptors in the retina and pigment epithelium

Abstract

Abstract Growth factors are regarded as factors to induce (or in some cases inhibit) growth of cells/tissues in vitro and/or in vivo . Molecules regarded as growth factors consist of six groups: the transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) and insulin-like growth factor (IGF). In an attempt to introduce clinical implications of such factors in ocular diseases, in this review article, we describe the expression of growth factors and their receptors in the neural retina and retinal pigment epithelium (RPE). Also, the expression, clinical implications and therapeutic potential influence of such factors in a number of ocular diseases, such as proliferative vitreoretinopathy (PVR), epiretinal membranes, macular holes, diabetic retinopathy and retinal degeneration, are discussed. In summary, TGF-β is expressed in RPE cells under a variety of conditions, and is thought to enhance various processes in the pathogenesis of PVR in several ways such as stimulating cell-mediated gel contraction, modifying mitogenic effects of other growth factors and enhancing extracellular matrix production and the resultant fibrosis reaction. In part because of these diverse effects, TGF-β is a good candidate for adjunct use with vitrectomy for the treatment of macular holes. PDGF is another growth factor that is thought to be involved in the onset of proliferative intraocular diseases such as epiretinal membranes and PVR. PDGF is a potent mitogenic and chemotactic factor for retina-derived cells. With respect to proliferative diabetic retinopathy in particular, recent developments in clinical and basic research on the angiogenic effects of VEGF, which is also a member of PDGF family, have drawn much attention from investigators. So-called eye- and retina-derived growth factors have been shown to be identical to FGF. In both retina and RPE cells, FGF is known to induce a variety of changes in cellular proliferation, differentiation and in vivo angiogenesis. In addition to these changes, FGF is a promising neuroprotective drug against some retinal degenerative diseases. There is currently limited information on the relationship of differentiation of retinal precursor cells in the developing retina and EGF/TFG-α. Further studies on its physiological and pathological significance in the retina and RPE are required. IGF and insulin also are thought to play important roles in the development of diabetic retinopathy. Recent insight into the effects of VEGF, in addition to those of IGF/insulin, has modified our thinking of contribution of this growth factor to the proliferative and angiogenic response of the retina in diabetes. Taken together, our knowledge of the effects of growth factors on the eye has advanced dramatically because of the recent advances in molecular biology and cell biology. A number of investigators around the world are currently performing intensive research in an attempt to understand the significance of these various factors in the pathogenesis of ocular diseases. It is reasonable to assume that novel concepts in the treatment of many refractory ocular diseases will result from such studies.