Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Choi, Soyoung; Guo, Li; Cordeiro, M. Francesca

doi:10.3390/cells10061507

Cited by 32 publications

(42 citation statements)

References 135 publications

(359 reference statements)

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“…To note, the 5′UTR CD86 rs11575853 was highlighted in the MS families under study and has been found associated with lower expression in several arterial tissues and brain regions of the MS-GWAS gene IQCB1 , which encodes for the nephrocystin NPHP5. An intriguing hypothesis is that the altered expression of NPHP5, involved in amaurosis and retinopathies [ 75 ], represents a potential link between retinal diseases and neurodegeneration [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

Scapoli

Ziliotto

Lunghi

et al. 2021

IJMS

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Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.

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Section: Discussionmentioning

confidence: 99%

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

Scapoli

Ziliotto

Lunghi

et al. 2021

IJMS

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“…Immunization with Cop-1 has been tested in many CNS neurodegenerative diseases, and its commercial product Copaxone ® has been approved by the US Food and Drug Administration (FDA) for the treatment of MS ( 157 ). Glaucoma shares common aspects of pathogenesis with MS, including generation and tissue deposition of common autoantibodies (anti-MBP) and activation of local microglial cells ( 45 , 158 ). Clinical examination with optical coherence tomography (OCT) also indicates a close relationship between retinal RGC damage and MS neuropathy ( 15 ).…”

Section: The Emerging Role Of T Cell-based Immune Modulation Therapy In the Treatment Of Glaucoma - A Lesson From Cns Neurodegenerative Dmentioning

confidence: 99%

T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration

Wang

Wei

2021

Front. Immunol.

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Glaucoma as the leading neurodegenerative disease leads to blindness in 3.6 million people aged 50 years and older worldwide. For many decades, glaucoma therapy has primarily focused on controlling intraocular pressure (IOP) and sound evidence supports its role in delaying the progress of retinal ganglial cell (RGC) damage and protecting patients from vision loss. Meanwhile, accumulating data point to the immune-mediated attack of the neural retina as the underlying pathological process behind glaucoma that may come independent of raised IOP. Recently, some scholars have suggested autoimmune aspects in glaucoma, with autoreactive T cells mediating the chief pathogenic process. This autoimmune process, as well as the pathological features of glaucoma, largely overlaps with other neurodegenerative diseases in the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In addition, immune modulation therapy, which is regarded as a potential solution for glaucoma, has been boosted in trials in some CNS neurodegenerative diseases. Thus, novel insights into the T cell-mediated immunity and treatment in CNS neurodegenerative diseases may serve as valuable inspirations for ophthalmologists. This review focuses on the role of T cell-mediated immunity in the pathogenesis of glaucoma and discusses potential applications of relevant findings of CNS neurodegenerative diseases in future glaucoma research.

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“…), there are little approved clinical treatments for retinal diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and retinitis pigmentosa (RP). However, intense research is being carried out targeting these pathologies using a wide variety of approaches [58][59][60][61][62][63]. Current strategies focus on slowing down or stop the initial triggers (e.g., AREDS supplementation, exercise, eating well, and smoking cessation in dry AMD, and anti-VEGF intraocular injections in wet AMD) [64,65], or focus on relieving the symptoms (e.g., lowering intraocular pressure (IOP) with prostaglandin analogues or beta blockers in glaucoma) [66].…”

Section: Cannabinoid Receptors In Retinal Diseasesmentioning

confidence: 99%

The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors

Bouskila

Bleau

Micaelo-Fernandes

et al. 2021

Cells

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The endocannabinoid (eCB) system has been found in all visual parts of the central ner-vous system and plays a role in the processing of visual information in many species, including monkeys and humans. Using anatomical methods, cannabinoid receptors are present in the monkey retina, particularly in the vertical glutamatergic pathway, and also in the horizontal GABAergic pathway. Modulating the eCB system regulates normal retinal function as demonstrated by electrophysiological recordings. The characterization of the expression patterns of all types of cannabinoid receptors in the retina is progressing, and further research is needed to elucidate their exact role in processing visual information. Typical cannabinoid receptors include G-protein coupled receptor CB1R and CB2R, and atypical cannabinoid receptors include the G-protein coupled receptor 55 (GPR55) and the ion channel transient receptor potential vanilloid 1 (TRPV1). This review focuses on the expression and localization studies carried out in monkeys, but some data on other animal species and humans will also be reported. Furthermore, the role of the endogenous cannabinoid receptors in retinal function will also be presented using intraocular injections of known modulators (agonists and antagonists) on electroretinographic patterns in monkeys. The effects of the natural bioactive lipid lysophosphatidylglucoside and synthetic FAAH inhibitor URB597 on retinal function, will also be described. Finally, the potential of typical and atypical cannabinoid receptor acti-vity regulation in retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinitis pigmentosa will be briefly explored.

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Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

Cited by 32 publications

References 135 publications

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration

The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors

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