Stanniocalcin-1 is a Modifier of Oxygen-Induced Retinopathy Severity

Lauren A. Dalvin, Mary Elizabeth Hartnett, Colin A. Bretz, Cheryl R. Hann, Ricky Z. Cui, Alan D. Marmorstein, David Sheikh-Hamad, Michael P. Fautsch, Gavin W. Roddy

Research output: Contribution to journalArticle

Abstract

Purpose/Aim: Abnormal activation of signaling pathways related to angiogenesis, inflammation, and oxidative stress has been implicated in the pathophysiology of retinopathy of prematurity (ROP), a leading cause of blindness in pre-term infants. Therapies for ROP include laser and anti-vascular endothelial growth factor agents. However, these therapies have side effects, and even with adequate treatment, visual acuity can be impaired. Novel therapeutic options are needed. Stanniocalcin-1 (STC-1) is a neuroprotective protein with anti-inflammatory and anti-oxidative stress properties. Rodent models of oxygen-induced retinopathy (OIR) were selected to determine whether STC-1 plays a role in the development of OIR. Materials and methods: STC-1 gene and protein expression was first evaluated in the Sprague Dawley rat OIR model that is most similar to human ROP. OIR was then induced in wild-type and Stc-1−/- mice. Retinas were isolated and evaluated for avascular and neovascular area on retinal flat mounts. Quantification of gene expression by quantitative real-time PCR was performed. VEGF was assayed by ELISA in media obtained from induced pluripotent stem-cell-derived retinal pigment epithelial (iPS-RPE) cells following treatment with recombinant STC-1. Results: STC-1 was significantly upregulated in a rat model of OIR compared to room air controls at the gene (P <.05) and protein (P <.001) level. Stc-1−/- OIR mice showed significantly worse ROP compared to wild-type mice as assessed by avascular (20.2 ± 2.4% vs 15.2 ± 2.5%; P =.02) and neovascular area (14.3 ± 2.7% vs 8.8 ± 3.7%; P <.05). Transcript levels of vascular endothelial growth factor-A were significantly higher in Stc-1−/- OIR mice compared to wild-type controls (P =.03). STC-1 reduced VEGF production in iPS-RPE cells (P =.01). Conclusions: STC-1 plays a role in the OIR stress response and development of pathologic vascular features in rodent OIR models by regulating VEGF levels.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalCurrent Eye Research
Volume45
Issue number1
DOIs
StatePublished - Jan 2 2020

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Keywords

  • Retinopathy of prematurity
  • STC-1
  • Stanniocalcin-1
  • oxygen induced retinopathy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Dalvin, L. A., Hartnett, M. E., Bretz, C. A., Hann, C. R., Cui, R. Z., Marmorstein, A. D., Sheikh-Hamad, D., Fautsch, M. P., & Roddy, G. W. (2020). Stanniocalcin-1 is a Modifier of Oxygen-Induced Retinopathy Severity. Current Eye Research, 45(1), 46-51. https://doi.org/10.1080/02713683.2019.1645184