title: Modulation of retinal Müller cells by complement receptor C5aR.
abstract: OBJECTIVE
  Müller cells, a major type of glial cell found in the eye, are postulated to play an important role in many retinal diseases, including diabetic retinopathy (DR). Complement is an integral part of innate immunity, and the activation of complement has been associated with retinal diseases. However, the role of complement in the regulation of Müller cell function remains unclear. We were trying to address these issues in this study.
  
  
  METHODS
  Using primary human Müller cells and a spontaneously immortalized human Müller cell line, we examined the expression of complement receptor C5aR both at mRNA and protein levels. Regulation of C5aR expression on Müller cells by prostaglandin E2 and by hyperglycemia, both of which are integrally involved in DR, were studied. Significance of C5aR on Müller cells was also investigated by examining relevant cytokine productions and their impacts on retinal endothelial cell proliferation/permeability after ligating the receptor using its ligand, C5a.
  
  
  RESULTS
  C5aR is constitutively expressed in human Müller cells. Prostaglandin E2 and hyperglycemia individually and synergistically upregulate C5aR expression in Müller cells. Signaling through C5aR on Müller cells upregulates production of IL-6 and VEGF, which promotes the proliferation of human retinal endothelial cells and increases their permeability.
  
  
  CONCLUSIONS
  These results indicate that complement can regulate Müller cells through C5aR, which may contribute to the pathogenesis of retinal diseases, including DR.
authors.affiliation: Department of Pathology, Sichuan University, Chengdu, China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Cheng
authors.forename: Hong
authors.initials: H
authors.lastname: Bu
authors.forename: Jose-Andres C
authors.initials: JA
authors.lastname: Portillo
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Subauste
authors.forename: Suber S
authors.initials: SS
authors.lastname: Huang
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Kern
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C488033:C5AR1 protein, human; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement
keywords: diabetic retinopathy; innate immunity; retina