Protective effects of a composition of Chinese herbs- Gurigumu-13 on retinal ganglion cell apoptosis in DBA/2J glaucoma mouse model

AIM： To explore the concrete mechanism of a Mongolian compound medicine-Gurigumu-13 （GRGM） for glaucoma treatment. METHODS： DBA/2J mice, as glaucoma models, were intragastric administrated with GRGM to study the effect of GRGM on retinal ganglion cells （RGCs）. The loss of RGCs was evaluated with the number of RGCs and axons. The expression of the target protein of RGCs or mouse retinas was determined by Western blot. The relative content of malondialdehyde （MDA） was examined by ELISA assay. RESULTS： GRGM distinctly improved retina damage via increasing the number of neurons, RGCs and axons in a concentration dependent manner. Meanwhile, GRGM obviously decreased the high level of MDA and the expression of oxidative stress-related proteins in retinas of DBAJ2J mice, but promoted the expression of antioxidant proteins. Additionally, GRGM also significantly inhibited the protein expression of Bip and Chop, which were markers of endoplasmic reticulum stress-induced apoptosis. CONCLUSION： GRGM have obvious protective effects on RGCs in DBA/2J mice, and increase the number of RGCs and axons via inhibiting oxidative stress and endoplasmic reticulum stress.

Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing

AIM:To determine the effects of safranal on choroidal neovascularization(CNV)and oxidative stress damage of human choroidal microvascular endothelial cells(HCVECs)and its possible mechanisms.METHODS:Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of safranal(0.5 mg/kg·d,intraperitoneally)on CNV.CNV leakage on fluorescein angiography(FA)and CNV thickness on histology was compared.HCVECs were used for a H_(2)O_(2)-induced oxidative stress model to test the effect of safranal in vitro.MTT essay was carried to test the inhibition rate of safranal on cell viability at different concentrations.Tube formation was used to test protective effect of safranal on angiogenesis at different concentrations.mRNA transcriptome sequencing was performed to find the possible signal pathway.The expressions of different molecules and their phosphorylation level were validated by Western blotting.RESULTS:On FA,the average CNV leakage area was 0.73±0.49 and 0.31±0.11 mm^(2)(P=0.012)in the control and safranal-treated group respectively.The average CNV thickness was 127.4±18.75 and 100.6±17.34μm(P=0.001)in control and safranal-treated group.Under the condition of oxidative stress,cell proliferation was inhibited by safranal and inhibition rates were 7.4%-35.4%at the different concentrations.For tube formation study,the number of new branches was 364 in control group and 35,42,and 17 in 20,40,and 80μg/mL safranal groups respectively(P<0.01).From the KEGG pathway bubble graph,the PI3K-AKT signaling pathway showed a high gene ratio.The protein expression was elevated of insulin receptor substrate(IRS)and the phosphorylation level of PI3K,phosphoinositide-dependent protein kinase 1/2(PDK1/2),AKT and Bcl-2 associated death promoter(BAD)was also elevated under oxidative stress condition but inhibited by safranal.CONCLUSION:Safranal can inhibit CNV both in vivo and in vitro,and the IRS-PI3K-PDK1/2-AKT-BAD signaling pathway is involved in the pathogenesis of CNV.

TMEM63B regulates postnatal development of cochlear sensory epithelia via thyroid hormone signaling

Sound transmission occurs in the cochlea,a complex and ingenious subdivision in the inner ear.The structure of the cochlea develops structurally and functionally by the time before two postnatal weeks(the time of hearing onset)in mice(Geal-Dor et al.,1993).Greater epithelial ridge(GER,also known as Kolliker's organ)is a transient cochlear structure containing a group of columnar epithelial supporting cells surrounding the inner hair cells(IHCs).