Pulmonary surfactant protein a is expressed in mouse retina by müuller cells and impacts neovascularization in oxygen-induced retinopathy

Faizah Bhatti, Genevieve Ball, Ronald Hobbs, Annette Linens, Saad Munzar, Rizwan Akram, Alistair J. Barber, Michael Anderson, Michael Elliott, Madeline Edwards

Research output: Contribution to journalArticle

8 Scopus citations

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 (M¨uller 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 NFjB signaling) null mouse retinas and Müuller 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 Müuller 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 NFjB pathway and upregulated 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.

Original languageEnglish (US)
Pages (from-to)232-242
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number1
DOIs
StatePublished - Nov 18 2015

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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