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

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.

The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation

“…Among the 12 candidate compounds with a neuroprotective effect, hesperidin was notable for the strength of its neuroprotective effect (among the top 5; Supplementary Table 1 ) and good repeatability (Supplementary Figure 1 ). Taken together with many previous reports showing that hesperidin has anti-apoptotic, anti-oxidative stress and anti-inflammatory effects 27 – 34 , we thus considered that hesperidin was the best candidate for further study.…”

Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia

“…In retinal degeneration, gliosis of Müller cells down-regulates their cytoprotective function and contributes to edema development, neuronal hyperexcitation and glutamate toxicity, which is a major cause of neuronal degeneration [ 28 ]. Increased immunoreactivity for GFAP is a well-known marker for gliosis, especially in Müller cells [ 29 ]. Our research indicated that T0 treatment significantly reduced the expression of GFAP in the retina of rd1 mice, which suggested that T0 alleviated gliosis of Müller cells, thus resulting in protection of the retina.…”

Changes in Ocular Hemodynamics after Carotid Artery Angioplasty and Stenting (CAAS) in Patients with Different Severity of Ocular Ischemic Syndrome

“…11,[13][14][15][16][17] Second, reperfusion, after long-term ischemia, could potentially cause further damage to visual function. Akito Shimouchi 18 reported in his study that post-ischemic retinal reperfusion could further induce damage to retinal ganglion cells especially for eyes with prolonged ischemia and further could cause further damage to visual function. The third potential mechanism would be the retinal arteriolar occlusion highly related to HT, diabetes mellitus (DM), or hyperlipidemia.…”