title: Wnt modulators in the aqueous humor are associated with outer retinal damage severity in patients with neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To investigate the associations of the Wnt modulators Wnt inhibitory factor 1 (WIF-1) and Dickkopf 3 (DKK-3) in the aqueous humor with neovascular age-related macular degeneration (nAMD) and to determine their clinical implications.
  
  
  METHODS
  Seventy-four nAMD patients initially treated with an intravitreal injection of ranibizumab (IVR) and 74 age- and sex-matched controls were studied. Aqueous humor WIF-1 and DKK-3 levels were measured by Western blotting and an ELISA before and 1 month after two consecutive IVRs (pre- and post-IVR). Visual acuity assessments and spectral domain optical coherence tomography were performed pre- and post-IVR.
  
  
  RESULTS
  Western blotting showed increased WIF-1 and DKK-3 in 12 nAMD patients compared with 12 controls. The ELISA analysis demonstrated elevated WIF-1 (pre) and DKK-3 (pre) in 62 patients compared with 62 controls (54.7 vs. 23.0 and 114.3 vs. 93.0 ng/mL, respectively). In multivariate analyses, high WIF-1 (pre) levels were associated with increased disruption in the photoreceptor junction's inner and outer segments (IS/OS) (pre and post) and high WIF-1 (post) levels. Interestingly, WIF-1 (pre) levels were significantly higher in type 3 neovascularization (NV) patients than in type 1 or 2 NV (90.5 ± 36.7 vs. 48.3 ± 22.5 and 41.3 ± 28.8 ng/mL, respectively). However, choroidal thickness was not correlated with WIF-1 levels.
  
  
  CONCLUSIONS
  We report, for the first time, the possibility of phenotypic, anatomic, and ocular proteomic correlations, demonstrating correlated WIF-1 and DKK-3 upregulation in nAMD patients' aqueous humor. Secreted WIF-1, reflecting the degree of retinal structure damage, may be a new biomarker for the retina's healthy and disease states.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Ae Jin
authors.initials: AJ
authors.lastname: Choi
authors.affiliation: Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Jeehyun
authors.initials: J
authors.lastname: Yoon
authors.affiliation: Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Daehan
authors.initials: D
authors.lastname: Lim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Korea Department of Ophthalmology, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Hyung Chan
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Korea Department of Ophthalmology, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Chung
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001082:Aqueous Humor / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D018925:Chemokines; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000069579:Ranibizumab; D012097:Repressor Proteins / Q000378:metabolism*; D015854:Up-Regulation; D014792:Visual Acuity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C485569:WIF1 protein, human; D000069579:Ranibizumab
keywords: CNV; Wnt; age-related macular degeneration; aqueous humor; optical coherence tomography