title: Identification of urinary biomarkers for age-related macular degeneration.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) can be considered as a chronic low-grade systemic inflammatory disease. This study was undertaken to test the associations of AMD with the urinary proinflammatory cytokines transforming growth factor (TGF)-β1, macrophage chemoattractant protein (MCP)-1 and C3a-desArg, as potential noninvasive biomarkers for monitoring AMD.
  
  
  METHODS
  A cross-sectional study of 103 AMD cases, comprising early AMD (n = 51), geographic atrophy (GA; n = 19), or choroidal neovascularization (CNV; 33), and 54 unrelated controls, aged 73 ± 9 years, who attended the Royal Victorian Eye and Ear Hospital and private practice in Victoria, Australia. AMD status was determined from the bilateral retinal digital photographs and through angiography and optical coherence tomography images when confirmation of CNV was needed. Serum and urine cytokine levels were measured by immunoassay and the rs1061170 (Y402H) single-nucleotide polymorphism of the complement factor H (CFH) gene was determined.
  
  
  RESULTS
  Multivariate logistic regression analyses demonstrated significant associations of urinary TGF-β1 levels (odds ratio [95% confidence interval]: OR = 1.24 [1.02-1.50]; P < 0.031) and MCP-1 levels (OR = 1.07 [1.02-1.12]; P < 0.008), in early AMD, and also MCP-1 levels with GA (OR = 1.10 [1.03-1.17]; P < 0.003). There was no correlation between urinary and serum cytokine levels. Individuals with one or more copies of the C allele (Y402H) were 2.5 times more likely to have urinary MCP-1 above median levels (P < 0.040).
  
  
  CONCLUSIONS
  This study demonstrates a novel finding of an association between elevated urinary cytokines TGF-β1 and MCP-1 and AMD. Further development of a urinary biomarker profile could provide a practical tool for detection of early AMD, progression monitoring, and assessment of treatment efficacy.
authors.affiliation: Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia. rhg@unimelb.edu.au
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.forename: Lingwei W
authors.initials: LW
authors.lastname: Tao
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Goh
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.forename: Olga
authors.initials: O
authors.lastname: Ischenko
authors.forename: Liubov D
authors.initials: LD
authors.lastname: Robman
authors.forename: KhinZaw
authors.initials: K
authors.lastname: Aung
authors.forename: Tania
authors.initials: T
authors.lastname: Cipriani
authors.forename: Melinda
authors.initials: M
authors.lastname: Cain
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
authors.forename: Robyn
authors.initials: R
authors.lastname: Langham
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000706:Anaphylatoxins; D015415:Biomarkers / Q000652:urine*; D018932:Chemokine CCL2 / Q000652:urine*; D015926:Complement C3a / Q000652:urine*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007118:Immunoassay; D008268:Macular Degeneration / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D053773:Transforming Growth Factor beta1 / Q000652:urine*; D014739:Victoria / Q000453:epidemiology
chemical_list: D000706:Anaphylatoxins; D015415:Biomarkers; D018932:Chemokine CCL2; D053773:Transforming Growth Factor beta1; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a