An arylidene-thiazolidinedione derivative, GPU-4, without PPARγ activation, reduces retinal neovascularization

Shinsuke Nakamura, Kei Hayashi, Haruka Takizawa, Tetsuji Murase, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hiroki Kakuta, Hideko Nagasawa, Hideaki Hara

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Retinal angiogenesis is a leading cause of blindness, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Vascular endothelial growth factor (VEGF) is one of the major angiogenesis factors, and induces endothelial cell proliferation and migration. VEGF stimulates NADPH oxidase to produce reactive oxygen species (ROS), and ROS induce the transcription factors and genes involved in angiogenesis. In the present study, we demonstrated that GPU-4, 5-arylidene-2,4-thiazolidinedione derivative, demonstrates anti-angiogenic activity regarding human retinal microvascular endothelial cells (HRMECs) and retinal neovascularization in a mouse model of retinopathy of prematurity. GPU-4 inhibited the VEGF-induced radicals, proliferation, and migration in HRMECs without a PPARγ-mediated effect. Furthermore, systemic administration of GPU-4 inhibited the development of retinal neovascularization in a murine oxygen-induced retinopathy model but did not exert revascularization of the capillary-free area, which shows normal physiological revascularization. These findings indicate that GPU-4 suppressed in vitro and in vivo retinal neovascularization partly by a radical scavenging effect, suggesting that GPU-4 might be a potential therapeutic agent candidate for proliferative diseases of the retinal vasculature.

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalCurrent Neurovascular Research
Volume8
Issue number1
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Retinal Neovascularization
Peroxisome Proliferator-Activated Receptors
Vascular Endothelial Growth Factor A
Retinopathy of Prematurity
Endothelial Cells
Reactive Oxygen Species
Retinal Diseases
NADPH Oxidase
Angiogenesis Inducing Agents
Macular Degeneration
Diabetic Retinopathy
Blindness
Human Activities
Cell Movement
Transcription Factors
Cell Proliferation
Oxygen
Genes
2,4-thiazolidinedione
Therapeutics

Keywords

  • Anti-oxidative effect
  • Human retinal microvascular endothelial cell
  • Oxygen-induced retinopathy model
  • Reactive oxygen species
  • Thiazolidinedione
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

An arylidene-thiazolidinedione derivative, GPU-4, without PPARγ activation, reduces retinal neovascularization. / Nakamura, Shinsuke; Hayashi, Kei; Takizawa, Haruka; Murase, Tetsuji; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kakuta, Hiroki; Nagasawa, Hideko; Hara, Hideaki.

In: Current Neurovascular Research, Vol. 8, No. 1, 02.2011, p. 25-34.

Research output: Contribution to journalArticle

Nakamura, S, Hayashi, K, Takizawa, H, Murase, T, Tsuruma, K, Shimazawa, M, Kakuta, H, Nagasawa, H & Hara, H 2011, 'An arylidene-thiazolidinedione derivative, GPU-4, without PPARγ activation, reduces retinal neovascularization', Current Neurovascular Research, vol. 8, no. 1, pp. 25-34. https://doi.org/10.2174/156720211794520224
Nakamura, Shinsuke ; Hayashi, Kei ; Takizawa, Haruka ; Murase, Tetsuji ; Tsuruma, Kazuhiro ; Shimazawa, Masamitsu ; Kakuta, Hiroki ; Nagasawa, Hideko ; Hara, Hideaki. / An arylidene-thiazolidinedione derivative, GPU-4, without PPARγ activation, reduces retinal neovascularization. In: Current Neurovascular Research. 2011 ; Vol. 8, No. 1. pp. 25-34.
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