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Siponimod exerts neuroprotective effects on the retina and higher visual pathway through neuronal S1PR1 in experimental glaucoma

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Neural Regeneration Research 2023年第4期18卷 840-848页

作者： Devaraj Basavarajappa Vivek Gupta nitin chitranshi Roshana Vander Wall Rashi Rajput Kanishka Pushpitha Samridhi Sharma Mehdi Mirzaei Alexander Klistorner Stuart L.Graham Department of Clinical Medicine Faculty of MedicineHealth and Human SciencesMacquarie UniversityNorth RydeSydneyNSWAustralia

Sphingosine-1-phosphate receptor(S1PR)signaling regulates diverse pathophysiological processes in the central nervous *** role of S1PR signaling in neurodegenerative conditions is still largely *** is a specific modulator of S1P1 and S1P5 receptors,an immunosuppressant drug for managing secondary progressive multiple *** investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate ***-specific deletion of sphingosine-1-phosphate receptor(S1PR1)was carried out by expressing ***-Cre recombinase under Syn1 promoter in S1PR1mice to define the role of S1PR1 in *** retinal electrophysiological responses,along with histological and immunofluorescence analysis of the retina and optic nerve tissues,indicated significant neuroprotective effects of siponimod when administered orally via diet in chronic and acute optic nerve injury ***,siponimod treatment showed significant protection against trans-neuronal degenerative changes in the higher visual center of the brain induced by optic nerve *** treatment also reduced microglial activation and reactive gliosis along the visual *** results showed that siponimod markedly upregulated neuroprotective Akt and Erk1/2 activation in the retina and the ***-specific deletion of S1PR1 enhanced retinal and dorsolateral geniculate nucleus degenerative changes in a chronic optic nerve injury condition and attenuated protective effects of *** summary,our data demonstrated that S1PR1signaling plays a vital role in the retinal ganglion cell and dorsolateral geniculate nucleus neuronal survival in experimental glaucoma,and siponimod exerts direct neuroprotective effects through S1PR1 in neurons in the central nervous system independent of its peripheral immuno-modulatory *** findings s

关键词： glaucoma intraocular pressure neurodegeneration neuroprotection optic nerve injury retinal ganglion cells siponimod sphingosine-1-phosphate

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Retinal thickness and vascular parameters using optical coherence tomography in Alzheimer's disease:a meta-analysis

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Neural Regeneration Research 2023年第11期18卷 2504-2513页

作者： Samran Sheriff Ting Shen Sandra Abdal Danit Saks Mehdi Mirzaei Veer Gupta nitin chitranshi Yuyi You Angela Schultz Stuart L.Graham Vivek Gupta Macquarie Medical School Macquarie UniversitySydneyNSWAustralia Save Sight Institute The University of SydneySydneyNSWAustralia School of Medicine Deakin UniversityMelbourneVICAustralia

Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer’s disease-related changes in participants at various stages of the *** this metaanalysis,we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer’s disease and whether retinal measurements can be used to diffe rentiate between Alzheimer’s disease and control *** databases including Google Schola r,Web of Science,and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer’s disease and control ***-three studies(5850 participants,including 2249 Alzheimer’s disease patients and 3601controls) were included in this *** to controls,Alzheimer’s disease patients had a significantly lower global retinal nerve fiber layer thickness(standardized mean difference [SMD]=-0.79,95% confidence intervals [CI]:-1.03 to-0.54,P <0.00001) as well as each quadrant being thinner in Alzheimer’s disease versus *** macular paramete rs,values measured by optical coherence tomography were significantly lower in Alzheimer’s disease than controls for macular thickness(pooled SMD:-0.44,95% CI:-0.67 to-0.20,P=0.0003),foveal thickness(pooled SMD=-0.39,95% CI:-0.58 to-0.19,P <0.0001),ganglion cell inner plexiform layer(SMD=-1.26,95% CI:-2.24 to-0.27,P=0.01) and macular volume(pooled SMD=-0.41,95% CI-0.76 to-0.07,P=0.02).Analysis using optical coherence tomography angiography parameters revealed mixed results between Alzheimer’s disease and *** vessel density(pooled SMD=-0.42,95% CI:-0.68 to-0.17,P=0.0001) and deep vessel density(pooled SMD=-0.46,95% CI:-0.75 to-0.18,P=0.001) were found to be thinner in Alzheimer’s disease patients whereas the foveal avascular zone(SMD=0.84,95% CI:0.17-1.51,P=0.01) was larger in *** density and thickness of variou

关键词： Alzheimer’s disease foveal avascular zone macular thickness optical coherence tomography optical coherence tomography angiography retina retinal nerve fiber layer vessel density

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