The aim of study was to establish a mouse model of blue light emitting diode (LED) light-induced retinal damage and to evaluate the effects of the antioxidant N-acetylcysteine (NAC). Mice were ...exposed to 400 or 800 lx blue LED light for 2 h, and were evaluated for retinal damage 5 d later by electroretinogram amplitude and outer nuclear layer (ONL) thickness. Additionally, we investigated the effect of blue LED light exposure on shorts-wave-sensitive opsin (S-opsin), and rhodopsin expression by immunohistochemistry. Blue LED light induced light intensity dependent retinal damage and led to collapse of S-opsin and altered rhodopsin localization from inner and outer segments to ONL. Conversely, NAC administered at 100 or 250 mg/kg intraperitoneally twice a day, before dark adaptation and before light exposure. NAC protected the blue LED light-induced retinal damage in a dose-dependent manner. Further, blue LED light-induced decreasing of S-opsin levels and altered rhodopsin localization, which were suppressed by NAC. We established a mouse model of blue LED light-induced retinal damage and these findings indicated that oxidative stress was partially involved in blue LED light-induced retinal damage.
Our eyes are increasingly exposed to light from the emitting diode (LED) light of video display terminals (VDT) which contain much blue light. VDTs are equipped with televisions, personal computers, ...and smart phones. The present study aims to clarify the mechanism underlying blue LED light-induced photoreceptor cell damage. Murine cone photoreceptor-derived cells (661 W) were exposed to blue, white, or green LED light (0.38 mW/cm(2)). In the present study, blue LED light increased reactive oxygen species (ROS) production, altered the protein expression level, induced the aggregation of short-wavelength opsins (S-opsin), resulting in severe cell damage. While, blue LED light damaged the primary retinal cells and the damage was photoreceptor specific. N-Acetylcysteine (NAC), an antioxidant, protected against the cellular damage induced by blue LED light. Overall, the LED light induced cell damage was wavelength-, but not energy-dependent and may cause more severe retinal photoreceptor cell damage than the other LED light.
Abstract
After intracranial hemorrhage (ICH), iron is released from the hematoma and induces secondary brain injury. However, the detail effect of iron on blood-brain barrier (BBB) function is still ...unknown. We investigated whether hemoglobin (Hb), ferrous ammonium sulfate (FAS) or hemin which contains iron have the detrimental effect on both human brain microvascular endothelial cells and pericytes by cellular function analysis
in vitro
. We developed an iron (Fe
2+
)-detectable probe, Si-RhoNox-1, to investigate intracellular Fe
2+
accumulation (Fe
2+
intra
). After FAS treatment, there was the correlation between Fe
2+
intra
and cell death. Moreover, Hb or hemin treatment induced cell death, increased reactive oxygen species and promoted Fe
2+
intra
in both cells. These changes were inhibited by the Fe
2+
chelator, 2,2′-bipyridil (BP). Furthermore, hemin induced endothelial barrier dysfunction via disruption of junction integrity. Based on
in vitro
studies, we used a hemin-injection ICH mice model
in vivo
. Hemin injection (10 mM/10 µL, i.c.) induced deleterious effects including BBB hyper-permeability, neuronal deficits, neuronal damage, altered proteins expression, and Fe
2+
intra
in BBB composed cells. Lastly, BP (40 mg/kg, i.p.) administration attenuated neuronal deficits at 3 days after surgery. Collectively, Hb or hemin damaged BBB composed cells via Fe
2+
intra
. Therefore, the regulation of the Fe
2+
movement in BBB might be effective for treatment of ICH.
Abstract
The cornea is directly exposed to cigarette smoke, and smoking is a risk factor for several corneal diseases including dry eye syndrome. Currently, heated tobacco products (HTPs) are widely ...used as substitutes for cigarette smoking around the world. In the present study, we investigated the molecular mechanism(s) leading to cellular injury induced by cigarette smoke extract (CSE) or HTPs. Exposure to CSE perturbed the formation of tight junctions, leading to an increase in cell volume, a decrease in transepithelial electrical resistance (TER) in the human corneal epithelial cell-transformed (HCE-T) cell line. Moreover, CSE exposure induced both lipid peroxidation and ferrous Fe(II) ion accumulation in autolysosomal compartments. Interestingly, a cleaved form of ferritin appeared when HCE-T cells were incubated with CSE. This aberrant ferritin processing was suppressed by treatment with autophagy inhibitors. Furthermore, the CSE-induced cell death was suppressed by either ferrostatin-1 or deferoxamine (DFO). CSE exposure also promoted the expression of cytokines whereas DFO treatment inhibited the CSE-induced expression of these cytokines. Exposure to HTPs also induced both HCE-T cell death and cleaved ferritin accumulation in a concentration- and time-dependent manner. These results indicated that CSE or HTPs activated the ferroptosis signaling pathway, which contributed to corneal epithelial cell injury.
A new scheme using macroscopic coherence is proposed to experimentally determine the neutrino mass matrix, in particular the absolute value of neutrino masses, and the mass type, Majorana or Dirac. ...The proposed process is a collective, coherent Raman scattering followed by neutrino-pair emission from
|
e
⟩
of a long lifetime to
|
g
⟩
;
γ
0
+
|
e
⟩
→
γ
+
∑
ij
ν
i
ν
j
¯
+
|
g
⟩
with
ν
i
ν
j
¯
consisting of six massive neutrino-pairs. Calculated angular distribution has six (
ij
) thresholds which show up as steps at different angles. Angular locations of thresholds and event rates of the angular distribution make it possible to experimentally determine the smallest neutrino mass to the level of less than several meV, (accordingly all three masses using neutrino oscillation data), the mass ordering pattern, normal or inverted, and to distinguish whether neutrinos are of Majorana or Dirac type. Event rates of neutrino-pair emission, when the mechanism of macroscopic coherence amplification works, may become large enough for realistic experiments by carefully selecting certain types of target. The problem to be overcome is macro-coherently amplified quantum electrodynamic background of the process,
γ
0
+
|
e
⟩
→
γ
+
γ
2
+
γ
3
+
|
g
⟩
, when two extra photons,
γ
2
,
γ
3
, escape detection. We illustrate our idea using neutral Xe and trivalent Ho ion doped in dielectric crystals.
Diacylglycerol kinase (DGK) is an enzyme that converts diacylglycerol to phosphatidic acid. To date, 10 isoforms of DGKs (α, β, γ, δ, ε, ζ, η, θ, ι, and κ) have been identified in mammals, and these ...DGKs show characteristic expression patterns and roles. The expression levels of DGKs are comparatively higher in the central nervous system than in other organs and may play several important roles in regulating higher brain functions. Currently, many studies have been performed to reveal the roles of DGKs by knocking down or overexpression of DGKs in vitro. Additionally, knockout or overexpression mice of several DGKs have been generated, and phenotypes of these mice have been studied. In this review, we discuss the roles of DGKs in the central nervous system based on recent findings in genetic models.
Cilostazol is a phosphodiesterase-3 inhibitor and is known to have pleiotropic effects including antiplatelet and vasodilatation effects and protective effects on endothelial cells. Cilostazol also ...reportedly reduced stroke recurrence, poststroke intracranial hemorrhage, and extracranial bleeding in a meta-analysis. Although it is known that cilostazol has the potential to suppress hemorrhagic stroke, the precise mechanisms remained unclear. Therefore, we evaluated the protective effects and mechanisms of cilostazol against hemorrhagic stroke. We found that cilostazol prevented the hemorrhagic transformation induced by focal cerebral ischemia in mice treated with intravenous tissue plasminogen activator or warfarin via protecting endothelial cells and tight junction proteins. We also demonstrated that cilostazol attenuated collagenase-induced intracranial hemorrhage in mice. In vitro studies showed that endothelial cells, pericytes, tight junction proteins, adherence junction proteins, and the basement membrane, which are all components of the blood-brain barrier, were protected by the administration of cilostazol following collagenase injury. These results suggested that cilostazol reduces hemorrhagic stroke by protecting the entire blood-brain barrier. Here, we review the protective effects of cilostazol on the blood-brain barrier that result in the prevention of hemorrhagic stroke, discuss the results we obtained using multiple hemorrhagic stroke models, and introduce potential future applications of cilostazol.
The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is ...damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.
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