epidermal-growth-factor and Retinal-Degeneration

Topics: Adult; Aged; Aging; Alcoholism; Amino Acids; Anesthetics, Local; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Aqueous Humor; Autonomic Nervous System; Biological Transport, Active; Brain Chemistry; Cardiac Glycosides; Catecholamines; Cell Differentiation; Central Nervous System; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Epidermal Growth Factor; Eye; Fibrinolysis; Glaucoma; Granuloma; Graves Disease; Hallucinogens; Humans; Hypertension; Immunity, Cellular; Infant; Infant, Newborn; Leukotriene B4; Metabolism, Inborn Errors; Multiple Sclerosis; Muscle Relaxation; Nutritional Physiological Phenomena; Oxygen; Oxygen Consumption; Pigment Epithelium of Eye; Pineal Gland; Prostaglandin Antagonists; Prostaglandins; Psychotropic Drugs; Retina; Retinal Degeneration; Serotonin; Smoking; SRS-A; Stress, Physiological; Water-Electrolyte Balance

Contrasting with fish or amphibian, retinal regeneration from Müller glia is largely limited in mammals. In our quest toward the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP (Yes-associated protein), which is upregulated in Müller cells following retinal injury. Conditional Yap deletion in mouse Müller cells prevents cell-cycle gene upregulation that normally accompanies reactive gliosis upon photoreceptor cell death. We further show that, in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. In the mouse retina, where Müller cells do not spontaneously proliferate, YAP overactivation is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell proliferative response to injury and highlight a YAP-EGFR (epidermal growth factor receptor) axis by which Müller cells exit their quiescence state, a critical step toward regeneration.

Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Cycle; Cell Cycle Proteins; Cell Proliferation; Ependymoglial Cells; Epidermal Growth Factor; Humans; Mice, Inbred C57BL; Mice, Knockout; Neuroglia; Photoreceptor Cells, Vertebrate; Retina; Retinal Degeneration; Signal Transduction; Trans-Activators; Transcription, Genetic; Up-Regulation; Xenopus laevis; Xenopus Proteins; YAP-Signaling Proteins

Human CD93, an epidermal growth factor (EGF)-like domain containing transmembrane protein, is predominantly expressed in the vascular endothelium. Studies have shown that AA4, the homolog of CD93 in mice, may mediate cell migration and angiogenesis in endothelial cells. Soluble CD93 has been detected in the plasma of healthy individuals. However, the role of soluble CD93 in the endothelium remains unclear. Recombinant soluble CD93 proteins with EGF-like domains (rCD93D123, with domains 1, 2, and 3; and rCD93D23, with domains 2 and 3) were generated to determine their functions in angiogenesis. We found that rCD93D23 was more potent than rCD93D123 in stimulating the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Production of matrix-metalloproteinase 2 increased after the HUVECs were treated with rCD93D23. Further, in a tube formation assay, rCD93D23 induced cell differentiation of HUVECs through phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase and extracellular signal-regulated kinases-1/2 signaling. Moreover, rCD93D23 promoted blood vessel formation in a Matrigel-plug assay and an oxygen-induced retinopathy model in vivo. Our findings suggest that the soluble EGF-like domain containing CD93 protein is a novel angiogenic factor acting on the endothelium.

Topics: Animals; Cell Movement; Cell Proliferation; Collagen; Drug Combinations; Endothelial Cells; Endothelium, Vascular; Epidermal Growth Factor; Human Umbilical Vein Endothelial Cells; Humans; Laminin; Membrane Glycoproteins; Mice; Neovascularization, Pathologic; Oxygen; Protein Structure, Tertiary; Proteoglycans; Receptors, Complement; Retinal Degeneration; Signal Transduction

In RCS rats, the retinal pigment epithelium (RPE) is defective in phagocytosis of photoreceptor membranes. We have previously shown reduced expression of basic fibroblast growth factor (bFGF) in the RPE of 7-10-day-old RCS rats. This study using primary RPE cultures from rats of this age demonstrates that the phagocytic defect in the mutant RPE can be overcome by treatment with bFGF, by a mechanism involving gene transcription and that normal RPE phagocytosis, also requiring transcription, is blocked by a bFGF neutralizing antibody. The combined data point to a role for bFGF in the normal mechanism of RPE phagocytosis and the RCS defect.

Topics: Animals; Cells, Cultured; Epidermal Growth Factor; Fibroblast Growth Factor 2; Nerve Growth Factors; Phagocytosis; Pigment Epithelium of Eye; Rats; Rats, Mutant Strains; Retinal Degeneration