title: Angiogenic potential of vitreous from Proliferative Diabetic Retinopathy and Eales' Disease patients.
abstract: OBJECTIVE
  Proliferative Diabetic Retinopathy (PDR) and Eales' Disease (ED) have different aetiologies although they share certain common clinical symptoms including pre-retinal neovascularization. Since there is a need to understand if the shared end-stage angiogenic pathology of PDR and ED is driven by common stimulating factors, we have studied the cytokines contained in vitreous from both patient groups and analyzed the angiogenic potential of these samples in vitro.
  
  
  METHODS
  Vitreous samples from patients with PDR (n = 13) and ED (n = 5) were quantified for various cytokines using a cytokine biochip array and sandwich ELISA. An additional group of patients (n = 5) with macular hole (MH) was also studied for comparison. To determine the angiogenic potential of these vitreous samples, they were analyzed for their ability to induce tubulogenesis in human microvascular endothelial cells. Further, the effect of anti-VEGF (Ranibizumab) and anti-IL-6 antibodies were studied on vitreous-mediated vascular tube formation.
  
  
  RESULTS
  Elevated levels of IL-6, IL-8, MCP-1 and VEGF were observed in vitreous of both PDR and ED when compared to MH. PDR and ED vitreous induced greater levels of endothelial cell tube formation compared to controls without vitreous (P<0.05). When VEGF in vitreous was neutralized by clinically-relevant concentrations of Ranibizumab, tube length was reduced significantly in 5 of 6 PDR and 3 of 5 ED samples. Moreover, when treated with IL-6 neutralizing antibody, apparent reduction (71.4%) was observed in PDR vitreous samples.
  
  
  CONCLUSIONS
  We have demonstrated that vitreous specimens from PDR and ED patients share common elevations of pro-inflammatory and pro-angiogenic cytokines. This suggests that common cytokine profiles link these two conditions.
authors.affiliation: Department of Immunology and Cell Biology, Aravind Medical Research Foundation, Dr.G.Venkataswamy Eye Research Institute, Madurai, India.
authors.forename: Ponnalagu
authors.initials: P
authors.lastname: Murugeswari
authors.affiliation: Vitreous and Retina Service, Aravind Eye Care System, Madurai, India.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Shukla
authors.affiliation: Vitreous and Retina Service, Aravind Eye Care System, Madurai, India.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Kim
authors.affiliation: Vitreous and Retina Service, Aravind Eye Care System, Madurai, India.
authors.forename: Perumalsamy
authors.initials: P
authors.lastname: Namperumalsamy
authors.affiliation: Centre for Experimental Medicine, Queens University, Belfast, United Kingdom.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
authors.affiliation: Department of Immunology and Cell Biology, Aravind Medical Research Foundation, Dr.G.Venkataswamy Eye Research Institute, Madurai, India.
authors.forename: Veerappan
authors.initials: V
authors.lastname: Muthukkaruppan
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D015861:Retinal Neovascularization / Q000378:metabolism / Q000473:pathology*; D031300:Retinal Vasculitis / Q000378:metabolism / Q000473:pathology*; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D016207:Cytokines