title: Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia.
abstract: OBJECTIVE
  To characterize the angiogenic and inflammatory vitreous biomarker profiles in a spectrum of ischemic retinopathies, including neovascular glaucoma.
  
  
  METHODS
  This institutional review board-approved study retrospectively analyzed 80 undiluted vitreous samples obtained during pars vitrectomy. The specimens were frozen (-80°C) and sent for concentration analysis of 34 proteins by Bio-Plex Pro assays. Specimens were divided into four groups: patients undergoing epiretinal membrane (ERM) peeling and/or macular hole (MH) surgery with no history of diabetes (non-DM group), patients undergoing ERM peeling, and/or MH surgery with a history of diabetes (DM group), patients with proliferative diabetic retinopathy (PDR group), and patients with neovascular glaucoma (NVG group). Parametric and nonparametric analyses of demographics and cytokine levels were performed using SPSS.
  
  
  RESULTS
  There were no significant differences in demographics among cohorts. Numerous proteins were significantly elevated between non-DM and DM (G-CSF, sCD40L, Endoglin, IL-6, placental growth factor [PlGF], VEGF-D), DM and PDR (leptin, IL-8, PlGF, VEGF-A), and PDR and NVG (G-CSF, leptin, TIE-2, sCD40L, EGF, HB-EGF, IL-6, IL-8, PlGF, TNF-α). Only PlGF was significantly elevated between each successive cohort. The most potent drivers of NVG were PlGF, VEGF-A, IL-6, and IL-8.
  
  
  CONCLUSIONS
  While the role of angioproliferative growth factors is well documented in ischemic retinopathy, our study delineates the importance of inflammatory and previously underreported angiogenic proteins. It also demonstrates a significant incremental increase in certain factors with increasing levels of ischemia. Both of these findings may guide the development of future therapies for ischemic retinopathies.
authors.affiliation: Department of Ophthalmology and Visual Science Yale School of Medicine, New Haven, Connecticut, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Kovacs
authors.affiliation: University of California, San Diego School of Medicine, San Diego, California, United States.
authors.forename: Kyle V
authors.initials: KV
authors.lastname: Marra
authors.affiliation: Department of Ophthalmology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Gina
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Sushant
authors.initials: S
authors.lastname: Wagley
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Gianna C
authors.initials: GC
authors.lastname: Teague
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Namrata
authors.initials: N
authors.lastname: Nandakumar
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Kameran
authors.initials: K
authors.lastname: Lashkari
authors.affiliation: Department of Ophthalmology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Arroyo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D015355:Glaucoma, Neovascular / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D007511:Ischemia / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D012164:Retinal Diseases / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D012189:Retrospective Studies; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D015415:Biomarkers