並列タイトル等Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury
タイトル（掲載誌）Japanese Journal of Ophthalmology
一般注記First online: 25 September 2015
The final publication is available at Springer via http://dx.doi.org/10.1007/s10384-015-0415-z
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.
identifier:PMID:26407617
開始ページ : 51
終了ページ : 61
DOIinfo:doi/10.1007/s10384-015-0415-z
コレクション（個別）国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
受理日（W3CDTF）2016-11-02T12:02:18+09:00
連携機関・データベース国立国会図書館 : 国立国会図書館デジタルコレクション