title: Biomarkers for Diabetic Retinopathy - Could Endothelin 2 Be Part of the Answer?
abstract: OBJECTIVE
  The endothelins are a family of three highly conserved and homologous vasoactive peptides that are expressed across all organ systems. Endothelin (Edn) dysregulation has been implicated in a number of pathophysiologies, including diabetes and diabetes-related complications. Here we examined Edn2 and endothelin receptor B (Endrb) expression in retinae of diabetic mouse models and measured serum Edn2 to assess its biomarker potential.
  
  
  METHODS
  Edn2 and Ednrb mRNA and Edn2 protein expression were assessed in young (8wk) and mature (24wk) C57Bl/6 (wild type; wt), Kimba (model of retinal neovascularisation, RNV), Akita (Type 1 diabetes; T1D) and Akimba mice (T1D plus RNV) by qRT-PCR and immunohistochemistry. Edn2 protein concentration in serum was measured using ELISA.
  
  
  RESULTS
  Fold-changes in Edn2 and Ednrb mRNA were seen only in young Kimba (Edn2: 5.3; Ednrb: 6.0) and young Akimba (Edn2: 7.9, Ednrb: 8.8) and in mature Kimba (Edn2:9.2, Ednrb:11.2) and mature Akimba (Edn2:14.0, Ednrb:17.5) mice. Co-localisation of Edn2 with Müller-cell-specific glutamine synthetase demonstrated Müller cells and photoreceptors as the major cell types for Edn2 expression in all animal models. Edn2 serum concentrations in young Kimba, Akita and Akimba mice were not elevated compared to wt. However, in mature mice, Edn2 serum concentration was increased in Akimba (6.9pg/mg total serum protein) compared to wt, Kimba and Akita mice (3.9, 4.6, and 3.8pg/mg total serum protein, respectively; p<0.05).
  
  
  CONCLUSIONS
  These results demonstrated that long-term hyperglycaemia in conjunction with VEGF-driven RNV increased Edn2 serum concentration suggesting Edn2 might be a candidate biomarker for vascular changes in diabetic retinopathy.
authors.affiliation: Molecular Ophthalmology, Lions Eye Institute, Nedlands, WA, 6009, Australia.
authors.forename: Nicolette
authors.initials: N
authors.lastname: Binz
authors.affiliation: Molecular Ophthalmology, Lions Eye Institute, Nedlands, WA, 6009, Australia.|Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Rakoczy
authors.affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Ireni S
authors.initials: IS
authors.lastname: Ali Rahman
authors.affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Nermina N
authors.initials: NN
authors.lastname: Vagaja
authors.affiliation: Molecular Ophthalmology, Lions Eye Institute, Nedlands, WA, 6009, Australia.|Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, 6009, Australia.
authors.forename: Chooi-May
authors.initials: CM
authors.lastname: Lai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D019333:Endothelin-2 / Q000097:blood / Q000235:genetics*; D063928:Ependymoglial Cells / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006442:Glycated Hemoglobin / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D044023:Receptor, Endothelin B / Q000097:blood / Q000235:genetics*; D015861:Retinal Neovascularization / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019333:Endothelin-2; D006442:Glycated Hemoglobin; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D042461:Vascular Endothelial Growth Factor A; C000602969:EDNRB protein, mouse; C467480:vascular endothelial growth factor A, mouse