Inherited retinal degeneration (IRD) is a group of fundus diseases characterized by a high degree of genetic heterogeneity and clinical heterogeneity, and more than 300 genetic mutations have been identified in association with IRD. Dysregulation of the intracellular second messenger cyclic guanosine monophosphate (cGMP) plays an important role in the development of IRD. cGMP participates in phototransduction process in photoreceptors. Abnormally elevated cGMP over-activate protein kinase G and cyclic nucleotide-gated channel, causing protein phosphorylation and Ca 2+ overload, respectively, and these two cGMP-dependent pathways may individually or collectively drive photoreceptor degenerative lesions and death; therefore, reducing cGMP synthesis and blocking downstream signaling can be considered as treatment strategies. Investigating the molecular mechanisms of cGMP dysregulation in photoreceptor degeneration may provide a more comprehensive picture of the pathogenesis of IRD, as well as ideas for finding new therapeutic targets and designing therapeutic programs.

Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.

Objective To observe neuroprotective effects of Ca2+/calmodulin-dependent kinase Ⅱ(CaMKⅡ)γ and CaMkⅡ δ against acute neuronal ischemic reperfusion injury in mice and explore the underlying mechanism.Methods Primary cultures of brain neurons isolated from fetal mice(gestational age of 18 days)were transfected with two specific siRNAs(si-CAMK2G and si-CAMK2D)or a control sequence(si-NT).After the transfection,the cells were exposed to oxygen-glucose deprivation/reperfusion(OGD/R)conditions for 1 h followed by routine culture.The expressions of phosphatidylinositol-3-kinase/extracellular signal-regulated kinase(PI3K/Akt/Erk)signaling pathway components in the neurons were detected using immunoblotting.The expressions of the PI3K/Akt/Erk signaling pathway proteins were also detected in the brain tissues of mice receiving middle cerebral artery occlusion(MCAO)or sham operation.Results The neuronal cells transfected with si-CAMK2G showed significantly lower survival rates than those with si-NT transfection at 12,24,48,and 72 h after OGD/R(P<0.01),and si-CAMK2G transfection inhibited OGD/R-induced upregulation of CaMKⅡγ expression.Compared to si-NT,transfection with si-CAMK2G and si-CAMK2D both significantly inhibited the expressions of PI3K/Akt/Erk signaling pathway components(P<0.01).In the mouse models of MCAO,the expressions of CaMKⅡδ and CaMKⅡγ were significantly increased in the brain,where activation of the PI3K/Akt/Erk signaling pathway was detected.The expression levels of CaMKⅡδ,CaMKⅡγ,Erk,phosphorylated Erk,Akt,and phosphorylated Akt were all significantly higher in MCAO mice than in the sham-operated mice at 24,48,72,and 96 h after reperfusion(P<0.05).Conclusion The neuroprotective effects of CaMKⅡδ and CaMKⅡγ against acute neuronal ischemic reperfusion injury are mediated probably by the PI3K/Akt/Erk pathway.

Objective To investigate the relation between intrauterine growth and the development of carotid atherosclerosis in later life. Methods The intima-media thickness of carotid was measured with ultrasonography in 2036 people aged above fifty who had complete birth records, and divided into normal and abnormal group. They were asked to fill in the cardio-cerebrovascular questionnaire, and venous blood samples were taken and analysed for various biochemical parameters. The relation between carotid atherosclerosis and various parameters at birth and in adult life was assessed. Results The birthweight and head circumference in abnormal group were less than those in normal. The prevalence of carotid atherosclerosis was greatest in those weighed 2500g or less, whose risk of carotid atherosclerosis was greater than those weighed between 3000g and 3500g, after adjustment for cardiovascular risk factors. Conclusions Increased atherogenesis may be one independent mechanism mediating the epidemiological link between impaired fetal growth and vascular disease.