June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Interleukin 1 Beta reduces hypoxia, prevents neovascularisation and promotes healthy vascular regeneration in oxygen induced retinopathy
Author Affiliations & Notes
  • Senthil Selvam
    Institute of Ophthalmology, University College London, London, United Kingdom
    NIHR Biomedical Research Centre, Moorfields Eye Hospital, London, United Kingdom
  • Andrew Scott
    NIHR Biomedical Research Centre, Moorfields Eye Hospital, London, United Kingdom
  • Monte J Radeke
    Neuroscience Research Institute , University of California Santa Barbara, Santa Barbara, California, United States
  • Marcus Fruttiger
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Senthil Selvam, None; Andrew Scott, None; Monte Radeke, None; Marcus Fruttiger, Amakem (F), Astra Zeneca (F), Fight For Sight (F), Novartis (C), Novartis (F)
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3451. doi:
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      Senthil Selvam, Andrew Scott, Monte J Radeke, Marcus Fruttiger; Interleukin 1 Beta reduces hypoxia, prevents neovascularisation and promotes healthy vascular regeneration in oxygen induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3451.

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

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Abstract

Purpose : We have previously found that activation of the inflammatory cascade in mice treated with lipopolysaccharide (LPS) protects against retinal hypoxia and neovascularisation associated with oxygen induced retinopathy (OIR). We hypothesised that LPS treatment leads to upregulation of pro-inflammatory cytokines in ischaemic retina which is then protective against the ensuing hypoxia.

Methods : To assess whether an increase in pro-inflammatory cytokine gene expression was seen in the ischaemic retina of LPS treated mice, transcriptional profiling using RNA sequencing was performed on central (vaso-obliterated) and peripheral (vascularised) retinal tissue, obtained from mice undergoing OIR treated with either LPS or phosphate buffered saline (PBS) . The cytokines found to be most upregulated were then injected intraocularly and intraperitoneally (IP) to assess their effect on OIR mice. Neovascularisation was assessed by measuring avascular area and area of neovascular tufts at P17. Hypoxia was assessed by measuring vessel tortuosity and EF5 hypoxia staining at P14.

Results : The most apparent increases in cytokines as a result of LPS treatment compared to the PBS control in the central retina were IL1β (72 fold), CCR1 (16 fold), CCL5 (13 fold) and CCR2 (13 fold). Intraocular injection of IL1β at P12 in OIR mice significantly reduced hypoxia at P14 and reduced neovascularisation at P17. In comparison, intraocular injection of CCL5 at P12 failed to reduced hypoxia at P14. Intraperitoneal injection of IL1β at P12 in OIR mice also significantly reduced hypoxia at P14. The reduced OIR phenotype seen in IL1β treated mice is the same as that seen in LPS treated mice.

Conclusions : IL1β is the main mediator of the protective effect LPS has on retinal hypoxia and neovascularisation associated with OIR. These findings are counterintuitive to the current literature and provide new insight into the role of IL1β on regulation of retinal oxygen demand. This novel approach of refined immunomodulation to reduce hypoxia has the potential to lead to novel therapies targeting hypoxia and preventing neovascularisation in ischaemic eye disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

IL1β IP injection at P12 after hyperoxia reduces hypoxia at P14 in OIR. Retinal wholemounts from P14 C57BL6 mice after OIR stained with isolectin B4 and EF5 hypoxia stain. IL1β injection reduced EF5 staining and retinal artery tortuosity.

IL1β IP injection at P12 after hyperoxia reduces hypoxia at P14 in OIR. Retinal wholemounts from P14 C57BL6 mice after OIR stained with isolectin B4 and EF5 hypoxia stain. IL1β injection reduced EF5 staining and retinal artery tortuosity.

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