Faizah Bhatti1, Genevieve Ball2, Ronald Hobbs3, Annette Linens2, Saad Munzar2, Rizwan Akram2, Alistair J Barber4, Michael Anderson5, Michael Elliott3, Madeline Edwards2. 1. 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. 2. Neonatal Perinatal Medicine, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States. 3. Department of Ophthalmology and Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States. 4. Department of Ophthalmology, Pennsylvania State University Hershey College of Medicine, Hershey, Pennsylvania, United States. 5. 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.
Abstract
PURPOSE: 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. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE: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. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
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