CULTURED HUMAN TRABECULAR MESHWORK CELLS EXPRESS FUNCTIONAL GROWTH-FACTOR RECEPTORS

PURPOSE. To compare the mRNA expression of growth factor receptors in cultured human trabecular meshwork (HTM) cells with ex vivo HTM tissue s and to determine whether HTM cells generate a physiologic response a fter exposure to exogenous growth factors. METHODS. The reverse transc ription-polymerase chain reaction (RT-PCR) method was used to detect t he expression of various growth factor receptor mRNAs using early pass aged, cultured HTM cells from donors of several ages. RT-PCR on ex viv o HTM tissues from healthy donors and donors with glaucoma were also u sed to compare and contrast mRNA expression with cell culture results. After the exogenous administration of growth factors, cell proliferat ion and extracellular acidification rate studies were used to measure the functional responses of HTM cells to growth factors. RESULTS. Ampl ification products of the expected size for 15 growth factor receptors were detected in cultured HTM cells and in ex vivo HTM tissues. The a dministration of exogenous growth factors showed that (a) hepatocyte g rowth factor (HGF), epidermal growth factor (EGF), insulinlike growth factor (IGF)-1, tumor necrosis factor (TNF) alpha, platelet-derived gr owth factor (PDGF)-AA, PDGF-BB, PDGF-AB, and basic fibroblast growth f actor (FGF-2) stimulated cell proliferation, whereas FGF-1 (acidic), t ransforming growth factor (TGF) alpha, interleukin (IL)-1 alpha, nerve growth factor (NGF), and FGF-7 (keratinocyte growth factor [KGF]) had no significant influence on cell proliferation; (b) TGF-beta isoforms significantly inhibited EGF-stimulated trabecular meshwork cell proli feration; and (c) FGF-1 (acidic), TGF alpha, EGF, IL-1 alpha, IL-1 bet a, HGF, TNF-alpha, PDGF-AA, and IGF-1 significantly stimulated extrace llular acidification, whereas FGF-2 (basic), FGF-7 (KGF), TGF-beta(1)- beta(3), and NGF had no significant influence on extracellular acidifi cation. CONCLUSIONS. These studies show that mRNA for numerous growth factor receptors can be detected in cultured HTM cells and in ex vivo HTM tissues. They also show that many of the receptors are functional, because exogenous growth factor administration elicits a physiologic response. In vivo, these receptors may be activated by growth factors present within the aqueous humor (aquecrine/paracrine) or by growth fa ctors synthesized and released locally by trabecular meshwork cells th emselves (autocrine). Specific growth factors acting through high-affi nity receptors may be involved in maintaining the normal microenvironm ent of the HTM and also may be involved in the pathogenesis of primary open-angle glaucoma.