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01.01.2016 | Laboratory Investigation

Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury

verfasst von: Akito Shimouchi, Harumasa Yokota, Shinji Ono, Chiemi Matsumoto, Toshihiro Tamai, Hiroko Takumi, Subbadra P. Narayanan, Shoji Kimura, Hiroya Kobayashi, Ruth B. Caldwell, Taiji Nagaoka, Akitoshi Yoshida

Erschienen in: Japanese Journal of Ophthalmology | Ausgabe 1/2016

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Abstract

Purpose

To determine whether water-dispersible hesperetin (WD-Hpt) can prevent degeneration of ganglion cell neurons in the ischemic retina.

Methods

Ischemia reperfusion (I/R) injury was induced by increasing the intraocular pressure of mice to 110 mmHg for 40 min. Mice received daily intraperitoneal injections with either normal saline (NS, 0.3 ml/day) or WD-Hpt (0.3 ml, 200 mg/kg/day). Reactive oxygen species (ROS) was assessed by dihydroethidium and nitrotyrosine formation. Inflammation was estimated by microglial morphology in the retina. Lipopolysaccharide (LPS)-stimulated BV-2 cells were used to explore the anti-inflammatory effect of WD-Hpt on activated microglia by quantifying the expression of IL-1β using real-time quantitative reverse transcription-polymerase chain reaction. Ganglion cell loss was assessed by immunohistochemistry of NeuN. Glial activation was quantified with glial fibrillary acidic protein (GFAP) immunoreactivity. Apoptosis was evaluated with a terminal deoxynucleotidyl transferase (TUNEL) assay and immunohistochemistry of cleaved caspase-3. Phosphorylation of extracellular signal-regulated kinase (p-ERK) was surveyed by western blotting.

Results

WD-Hpt decreased I/R-induced ROS formation. WD-Hpt alleviated microglial activation induced by I/R and reduced mRNA levels of IL-1β in LPS-stimulated BV-2. I/R resulted in a 37 % reduction in the number of ganglion cells in the NS-treated mice, whereas the reduction was only 5 % in the WD-Hpt-treated mice. In addition, WD-Hpt mitigated the immunoreactivity of GFAP, increased expression of cleaved caspase-3, increased number of TUNEL positive cells and p-ERK after I/R.

Conclusions

WD-Hpt protected ganglion cells from I/R injury by inhibiting oxidative stress and modulating cell death signaling. Moreover, WD-Hpt had an anti-inflammatory effect through the suppression of activated microglia.

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Titel: Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury
verfasst von: Akito Shimouchi
Harumasa Yokota
Shinji Ono
Chiemi Matsumoto
Toshihiro Tamai
Hiroko Takumi
Subbadra P. Narayanan
Shoji Kimura
Hiroya Kobayashi
Ruth B. Caldwell
Taiji Nagaoka
Akitoshi Yoshida
Publikationsdatum: 01.01.2016
Verlag: Springer Japan
Erschienen in: Japanese Journal of Ophthalmology / Ausgabe 1/2016
Print ISSN: 0021-5155
Elektronische ISSN: 1613-2246
DOI: https://doi.org/10.1007/s10384-015-0415-z

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Springer Medizin

Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

Purpose

Methods

Results

Conclusions

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