Valproic Acid Inhibits Human Retinal Pigment Epithelial (hRPE) Cell Proliferation Via a P38 MAPK Signaling Mechanism.

Valproic acid (VPA) has been reported to inhibit cancer cell growth and has therapeutic use in retinal diseases. However, the mechanism of this action remains unclear. In order to explore this mechanism, primary human retinal pigment epithelial (hRPE) cell cultures were established.

Valproic Acid Induced Human Retinal Pigment Epithelial Cell Death as Well as its Survival after Hydrogen Peroxide Damage is Mediated by P38 Kinase.

Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Several new drugs are now available to reduce the sight threatening complications of this disease, however, all are useful in only a small fraction of patients and none of them prevents disease development. An understanding of the pathogenesis of the retinal and macular degeneration is the first step in developing preventive and fully effective treatment options for this condition.

Impaired intracellular signaling may allow up-regulation of CTGF-synthesis and secondary peri-retinal fibrosis in human retinal pigment epithelial cells from patients with age-related macular degeneration.

Age-related macular degeneration (AMD) is a major sight-threatening ocular disorder in the United States of America and the world, yet its etiology is not clearly understood, preventing the development of effective prevention or therapy. Connective tissue growth factor (CTGF) has been implicated in the pathological synthesis of peri-retinal fibrous tissue in patients with AMD. Very little is known about the mechanism of this interaction.

MAP kinase pathway is involved in IGF-1-stimulated proliferation of human retinal pigment epithelial cells (hRPE).

Purpose: To investigate the mitogenic activity of insulin-like growth factor-1 (IGF-1) on the proliferation of human retinal pigment epithelial cells (hRPE) and to elucidate the role of vascular endothelial growth factor (VEGF) and MAP kinase (MAPK) in the IGF-1 signaling cascade.

Methods: Human RPE specimens were obtained from postmortem non-pathological eyes and cultured in vitro through several passages. Cellular proliferation in the presence of increasing concentrations of IGF-1 and IGF-1 + PD98059 (a known MAPK inhibitor) was measured by [(3)H]thymidine incorporation; trypan blue exclusion studies (T) verified cell viability.