June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Müller Cell Associated Surfactant Protein A Impairs Retinal Endothelial Cell Function
Author Affiliations & Notes
  • Faizah Bhatti
    Neonatal Perinatal Medicine, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, OK
    Ophthalmology, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, OK
  • Genevieve Ball
    Neonatal Perinatal Medicine, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, OK
  • Raja Akram
    Neonatal Perinatal Medicine, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, OK
  • Michael Elliott
    Ophthalmology, Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, OK
  • Footnotes
    Commercial Relationships Faizah Bhatti, None; Genevieve Ball, None; Raja Akram, None; Michael Elliott, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5558. doi:
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      Faizah Bhatti, Genevieve Ball, Raja Akram, Michael Elliott; Müller Cell Associated Surfactant Protein A Impairs Retinal Endothelial Cell Function. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5558.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Retinopathy of prematurity (ROP) research has mainly focused on hyperoxia/hypoxia related angiogenic signaling and altered nutritional status. The role of inflammatory signals is less established. Surfactant protein A (SP-A) is a c-type lectin known to interact with cytokines and macrophages particularly in lung disease of prematurity. We have previously demonstrated that SP-A is present in the mouse retina and that activation of toll like receptor 2 and 4 (TLR-2 and TLR-4) increases SP-A expression in vivo. We further aimed to elucidate the retinal cell types that express SP-A and study its effect on human retinal endothelial cell (HREC) function.

Methods: Retinas from C57B6/J mice were analyzed by fluorescent immunohistochemistry (IHC) with antibodies against SP-A and retinal cell markers including glutamine synthase (GS) for Müller cells, neurofilament M for ganglion cells, Rhodopsin for rods and cones and cd31 for blood vessels. In order to confirm SP-A expression, cultured immortalized human Müller cells (MIO-M1) were treated with TLR-2 and TLR-4 ligands and SP-A expression measured using ELISA. To study the effect of SP-A on HREC functions, cultured HREC’s were treated with purified SP-A and function was quantified by migration and proliferation assays.

Results: IHC results indicated co-localization of SP-A with GS in Müller cells in the mouse retina. Müller cell expression of SP-A was confirmed in vitro by quantifying SP-A expression in MIO-M1 cells after stimulating them with TLR-2 and TLR-4 ligands. SP-A expression peaked at 6 hours after treatment with LPS (p<0.001) and at 12 hours after stimulation with PamC3 (p<0.01). SP-A concentration in the media from the stimulated cells was also significantly increased compared to control media after treatment with PamC3 (p<0.001) and LPS (p<0.01). In endothelial cell function assays, HREC proliferation and migration were both significantly impaired after treatment with SP-A (p<0.01).

Conclusions: SP-A is expressed and secreted by mouse and human Müller cells and its expression is up regulated by TLR-2 and TLR-4 ligand stimulation. SP-A secreted by Müller cells impairs the migration and proliferation of HREC’s. These data suggest that SP-A is secreted by Müller cells in response to inflammatory signals and may impair retinal endothelial cell function, thus contributing to disorganized angiogenesis in the developing retina.

Keywords: 700 retinal neovascularization • 698 retinal development • 557 inflammation  
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