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In vivo imaging of structural,metabolic and functional brain changes in glaucoma

Neural Regeneration Research 2019年第3期14卷 446-449页

作者： Anisha Kasi muneeb a.faiq Kevin C.Chan NYU Langone Eye Center Department of Ophthalmology NYU School of Medicine NYU Langone Health New York University Department of Radiology NYU School of Medicine NYU Langone Health New York University Center for Neural Science Faculty of Arts and Science New York University

Glaucoma, the world's leading cause of irreversible blindness, is a condition for which elevated intraocular pressure is currently the only modifiable risk factor. However, the disorder can continue to progress even at reduced intraocular pressure. This indicates additional key factors that contribute to the etiopathogenesis. There has been a growing amount of literature suggesting glaucoma as a neurodegenerative disease of the visual system. However, it remains debatable whether the observed pathophysiological conditions are causes or consequences. This review summarizes recent in vivo imaging studies that helped advance the understanding of early glaucoma involvements and disease progression in the brains of humans and experimental animal models. In particular, we focused on the non-invasive detection of early structural and functional brain changes before substantial clinical visual field loss in glaucoma patients; the eye-brain interactions across disease severity; the metabolic changes occurring in the brain's visual system in glaucoma; and, the widespread brain involvements beyond the visual pathway as well as the potential behavioral relevance. If the mechanisms of glaucomatous brain changes are reliably identified, novel neurotherapeutics that target parameters beyond intraocular pressure lowering can be the promise of the near future, which would lead to reduced prevalence of this irreversible but preventable disease.

关键词： glaucoma intraocular pressure eye-brain-behavior relationship irreversible blindness magnetic resonance imaging metabolic brain changes sensitivity disease progression

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维普期刊数据库

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Glymphatic imaging and modulation of the optic nerve

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Neural Regeneration Research 2022年第5期17卷 937-947页

作者： Anisha Kasi Crystal Liu muneeb a.faiq Kevin C.Chan Department of Ophthalmology NYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Department of Radiology NYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Neuroscience Institute NYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Center for Neural Science College of Arts and ScienceNew York UniversityNew YorkNYUSA

Optic nerve health is essential for proper function of the visual ***,the pathophysiology of certain neurodegenerative disease processes affecting the optic nerve,such as glaucoma,is not fully ***,it was hypothesized that a lack of proper clearance of neurotoxins contributes to neurodegenerative *** ability to clear metabolic waste is essential for tissue homeostasis in mammals,including *** the brain lacks the traditional lymphatic drainage system identified in other anatomical regions,there is growing evidence of a glymphatic system in the central nervous system,which structurally includes the optic *** to acknowledge the supportive role of astroglial cells,this perivascular fluid drainage system is essential to remove toxic metabolites from the central nervous ***,we review existing literature describing the physiology and dysfunction of the glymphatic system specifically as it relates to the optic *** summarize key imaging studies demonstrating the existence of a glymphatic system in the optic nerves of wild-type rodents,aquaporin 4-null rodents,and humans;glymphatic imaging studies in diseases where the optic nerve is impaired;and current evidence regarding pharmacological and lifestyle interventions that may help promote glymphatic function to improve optic nerve *** conclude by highlighting future research directions that could be applied to improve imaging detection and guide therapeutic interventions for diseases affecting the optic nerve.

关键词： aquaporin-4 cerebrospinal fluid glaucoma glymphatic system hydrocephalus imaging metabolic waste clearance optic nerve perivascular pharmacological and lifestyle interventions

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维普期刊数据库

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Ocular manifestations of central insulin resistance

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Neural Regeneration Research 2023年第5期18卷 1139-1146页

作者： muneeb a.faiq Trina Sengupta Madhu Nath Thirumurthy Velpandian Daman Saluja Rima Dada Tanuj Dada Kevin C.Chan Dr.Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical SciencesNew DelhiIndia Neuroimaging and Visual Science Laboratory Department of OphthalmologyNYU Grossman School of MedicineNYU Langone HealthNew York UniversityNew YorkNYUSA Medical Biotechnology Laboratory Dr.B.R.Ambedkar Center for Biomedical ResearchUniversity of DelhiDelhiIndia Dr.Baldev Singh Sleep Laboratory Department of PhysiologyAll India Institute of Medical SciencesNew DelhiIndia Department of Ocular Pharmacology Dr.Rajendra Prasad Center for Ophthalmic SciencesAll India Institute of Medical SciencesNew DelhiIndia Laboratory for Molecular Reproduction and Genetics Department of AnatomyAll India Institute of Medical SciencesNew DelhiIndia

Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer’s disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most s

关键词： brain ciliary bodies gene expression inflammation insulin receptor insulin resistance intraocular pressure neurodegeneration optic nerve retina retinal ganglion cells trabecular meshwork

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