title: Pulmonary surfactant protein a is expressed in mouse retina by Müller cells and impacts neovascularization in oxygen-induced retinopathy.
abstract: OBJECTIVE
  Surfactant protein A (SP-A) up-regulates cytokine expression in lung disease of prematurity. Here we present data that for the first time characterizes SP-A expression and localization in the mouse retina and its impact on neovascularization (NV) in the mouse.
  
  
  METHODS
  Retinal SP-A was localized in wild-type (WT) mice with the cell markers glutamine synthetase (Müller cells), neurofilament-M (ganglion cells), glial acid fibrillary acid protein (astrocytes), and cluster of differentiation 31 (endothelial cells). Toll-like receptor 2 and 4 (TLR-2 and TLR-4) ligands were used to up-regulate SP-A expression in WT and myeloid differentiation primary response 88 (MyD88) protein (necessary for NFκB signaling) null mouse retinas and Müller cells, which were quantified using ELISA. Retinal SP-A was then measured in the oxygen-induced retinopathy (OIR) mouse model. The effect of SP-A on retinal NV was then studied in SP-A null (SP-A(-/-)) mice.
  
  
  RESULTS
  SP-A is present at birth in the WT mouse retina and colocalizes with glutamine synthetase. TLR-2 and TLR-4 ligands increase SP-A both in the retina and in Müller cells. SP-A is increased at postnatal day 17 (P17) in WT mouse pups with OIR compared to that in controls (P = 0.02), and SP-A(-/-) mice have reduced NV compared to WT mice (P = 0.001) in the OIR model.
  
  
  CONCLUSIONS
  Retinal and Müller cell SP-A is up-regulated via the NFκB pathway and up-regulated during the hypoxia phase of OIR. Absence of SP-A attenuates NV in the OIR model. Thus SP-A may be a marker of retinal inflammation during NV.
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States Department of Ophthalmology and Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Faizah
authors.initials: F
authors.lastname: Bhatti
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Ball
authors.affiliation: Department of Ophthalmology and Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Hobbs
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Annette
authors.initials: A
authors.lastname: Linens
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Saad
authors.initials: S
authors.lastname: Munzar
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Akram
authors.affiliation: Department of Ophthalmology, Pennsylvania State University Hershey College of Medicine, Hershey, Pennsylvania, United States.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Barber
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Anderson
authors.affiliation: Department of Ophthalmology and Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Elliott
authors.affiliation: Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
authors.forename: Madeline
authors.initials: M
authors.lastname: Edwards
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D010100:Oxygen
keywords: Müller cells; neovascularization; oxygen-induced retinopathy