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

Curr Eye Res. 2020 Jan;45(1):46-51. doi: 10.1080/02713683.2019.1645184. Epub 2019 Aug 28.

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.

Keywords: Retinopathy of prematurity; STC-1; Stanniocalcin-1; oxygen induced retinopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics*
  • Mice
  • Mice, Knockout
  • Oxidative Stress*
  • Oxygen / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Retinopathy of Prematurity / chemically induced
  • Retinopathy of Prematurity / genetics*
  • Retinopathy of Prematurity / metabolism
  • Signal Transduction
  • Up-Regulation*

Substances

  • Glycoproteins
  • teleocalcin
  • Oxygen