title: HTRA1 and TGF-β1 Concentrations in the Aqueous Humor of Patients With Neovascular Age-Related Macular Degeneration.
abstract: The purpose of this study was to evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), TGF-β1, bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and VEGFA proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to AMD.
  
  
  
  We measured by ELISA the concentrations of HTRA1, TGF-β1, BMP4, GDF6, and VEGFA in the aqueous humor of 23 patients affected by nCNV who received three consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). Twenty-three age-matched cataract patients served as controls.
  
  
  
  Bone morphogenetic protein 4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P < 0.0001) and higher than both the month 1 (P < 0.0001) and the month 2 (P < 0.0001) values. Baseline VEGFA was higher than controls (P < 0.0001), not different from month 1 value (P = 0.0821), but higher than month 2 value (P < 0.0001). Baseline TGF-β1 was higher than controls (P = 0.0015) and not different from month 1 (P = 0.129) and month 2 values (P = 0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-β1, HTRA 1 and VEGFA, or TGF-β1 and VEGFA.
  
  
  
  In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in neovascular AMD and a VEGFA-independent role for TGF-β1.
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Tosi
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Caldi
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Nuti
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Marigliani
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Baiocchi
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Traversi
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cevenini
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Tarantello
authors.affiliation: Ophthalmology Unit of the Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Fusco
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Nardi
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Orlandini
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Galvagni
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D001082:Aqueous Humor / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D011446:Prospective Studies; D000069579:Ranibizumab / Q000008:administration & dosage; D012697:Serine Endopeptidases / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D000069579:Ranibizumab