Demyelination of the Optic Nerve: An Underlying Factor in Glaucoma?

Xue, Jingfei; Zhu, Yingting; Zhe, Liu; Lin, Jicheng; Li, Yangjiani; Li, Yiqing; Zhuo, Yehong

doi:10.3389/fnagi.2021.701322

Cited by 12 publications

(6 citation statements)

References 99 publications

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“…Although all three of the non-neural retinal cell types have been discussed as contributors to glaucoma pathogenesis ( 24 , 75 ), mechanisms remain to be elucidated. Alterations in the ON in glaucoma have generally been viewed as consequences of axonal damage and loss, but our results support the hypothesis ( 76 ) that it may also play a causal role. The genes in this list provide entry points for further analysis.…”

Section: Discussionsupporting

confidence: 79%

Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye

Monavarfeshani

Yan

Pappas

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here, we used high-throughput single-nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in six extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases—for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ~151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the data presented here complete a “Version 1” cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as the neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.

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Section: Discussionsupporting

confidence: 79%

Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye

Monavarfeshani

Yan

Pappas

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“… 97 , 98 Demyelination may contribute to the pathogenesis of glaucoma and precede axonal degeneration. 99 – 101 A recent study explored the relationship between the rs12976445 polymorphism in miR-125 and POAG severity. 102 They compared 88 patients with POAG comprising 3 genotype groups (GG, GC, and CC) to evaluate the relationship between each group and the POAG index.…”

Section: Discussionmentioning

confidence: 99%

Exploring Early-Stage Retinal Neurodegeneration in Murine Pigmentary Glaucoma: Insights From Gene Networks and miRNA Regulation Analyses

Gu,

Kumar,

Hook

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Glaucoma is a group of heterogeneous optic neuropathies characterized by the progressive degeneration of retinal ganglion cells. However, the underlying mechanisms have not been understood completely. We aimed to elucidate the genetic network associated with the development of pigmentary glaucoma with DBA/2J (D2) mouse model of glaucoma and corresponding genetic control D2- Gpnmb (D2G) mice carrying the wild type (WT) Gpnmb allele. Methods Retinas isolated from 13 D2 and 12 D2G mice were subdivided into 2 age groups: pre-onset (1–6 months: samples were collected at approximately 1–2, 2–4, and 5–6 months) and post-onset (7–15 months: samples were collected at approximately 7–9, 10–12, and 13–15 months) glaucoma were compared. Differential gene expression (DEG) analysis and gene-set enrichment analyses were performed. To identify micro-RNAs (miRNAs) that target Gpnmb , miRNA expression levels were correlated with time point matched mRNA expression levels. A weighted gene co-expression network analysis (WGCNA) was performed using the reference BXD mouse population. Quantitative real-time PCR (qRT-PCR) was used to validate Gpnmb and miRNA expression levels. Results A total of 314 and 86 DEGs were identified in the pre-onset and post-onset glaucoma groups, respectively. DEGs in the pre-onset glaucoma group were associated with the crystallin gene family, whereas those in the post-onset group were related to innate immune system response. Of 1329 miRNAs predicted to target Gpnmb , 3 miRNAs (miR-125a-3p, miR-3076-5p, and miR-214-5p) were selected. A total of 47 genes demonstrated overlapping with the identified DEGs between D2 and D2G, segregated into their time-relevant stages. Gpnmb was significantly downregulated, whereas 2 out of 3 miRNAs were significantly upregulated ( P < 0.05) in D2 mice at both 3-and 10-month time points. Conclusions These findings suggest distinct gene-sets involved in pre-and post-glaucoma in the D2 mouse. We identified three miRNAs regulating Gpnmb in the development of murine pigmentary glaucoma.

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“…For the Practitioner демиелинизация и необратимая гибель нейронов [1]. Офтальмологические нейродегенеративные заболевания имеют тесную связь с системными нейродегенеративными процессами и изменениями в центральной нервной системе [2,3].…”

Section: практикующему врачуunclassified

Modern Approaches to Neuroprotection in Ophthalmic Neurodegenerative Diseases

Guzun¹,

Коновалова²,

Khramenko³

et al. 2022

Офтальмология. Восточная Европа

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Нейродегенеративные заболевания – это группа гетерогенных заболеваний с прогрессирующей и селективной потерей нейронов. Эти заболевания имеют некоторые общие патологические изменения, такие как аксональная дисфункция, демиелинизация и необратимая гибель нейронов. Офтальмонейродегенеративные заболевания имеют тесную связь с системными нейродегенеративными процессами и изменениями в центральной нервной системе. Поскольку распространенность нейродегенеративных заболеваний резко увеличивается с возрастом, а население стареет, эти процессы могут оказывать все большее влияние на качество жизни людей, что вызывает необходимость проведения нейропротекторной терапии.Окислительный стресс, ишемия, нейровоспаление и митохондриальная дисфункция приводят к гибели ганглиозных клеток сетчатки (ГКС) и являются основными причинами наиболее распространенных офтальмологических нейродегенеративных заболеваний, таких как глаукоматозная, ишемическая и диабетическая оптиконейропатии.Применение цитиколина при офтальмологических нейродегенеративных заболеваниях основано на его многофакторном механизме действия и участии в нескольких метаболических путях, включая гомеостаз фосфолипидов, митохондриальную динамику, а также холинергическую и дофаминергическую передачу импульса. Цитиколин стимулирует биосинтез сфингомиелина, способствующего стабилизации плазматической мембраны аксонов ГКС, и предотвращает высвобождение модуляторов нейровоспаления. А также, учитывая, что офтальмонейродегенерация сопровождается повышенным окислительным стрессом, а мозговой ткани для поддержания надлежащей электрофизиологической функции необходимы антиоксиданты, проникающие через гематоэнцефалический барьер, разумно предположить, что необходимы терапевтически-патогенетические стратегии, основанные на нейропротекции витаминно-антиоксидантным комплексом Цебролюкс™ НФ Нейрофактор, который будет обоснованно эффективен в замедлении гибели ГКС и сохранении их функции при офтальмонейродегенеративных заболеваниях. Neurodegenerative diseases are a group of heterogeneous diseases with progressive and selective loss of neurons. These diseases share some common pathological changes such as axonal dysfunction, demyelination, and irreversible neuronal death. Ophthalmic neurodegenerative diseases are closely related to systemic neurodegenerative processes and changes in the central nervous system.Since the prevalence of neurodegenerative diseases increases sharply with age, and the population ages, these processes can have an increasing impact on the quality of life of people, which necessitates neuroprotective therapy.Oxidative stress, neuroinflammation and mitochondrial dysfunction lead to the death of retinal ganglion cells and are the main causes of the most common ophthalmic neurodegenerative diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy.The use of citicoline in ophthalmic neurodegenerative diseases is based on its multifactorial mechanism of action and participation in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, and cholinergic and dopaminergic impulse transmission. Citicoline stimulates the biosynthesis of sphingomyelin, which helps to stabilize the plasma membrane of the axons of retinal ganglion cells (RGC) and prevents the release of neuroinflammation modulators. And also considering that neurodegenerative diseases are accompanied by increased oxidative stress, and brain tissue needs antioxidants that penetrate the blood-brain barrier to maintain proper electrophysiological function, it is reasonable to assume that therapeutic and pathogenetic strategies are needed based on neuroprotection with the neurotropic vitamin-antioxidant complex Cebrolux™ NF NeuroFactor will be effective in slowing the death of GCS in neurodegenerative diseases such as glaucoma, ischemic optic neuropathy and diabetic retinopathy.

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Demyelination of the Optic Nerve: An Underlying Factor in Glaucoma?

Cited by 12 publications

References 99 publications

Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye

Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye

Exploring Early-Stage Retinal Neurodegeneration in Murine Pigmentary Glaucoma: Insights From Gene Networks and miRNA Regulation Analyses

Modern Approaches to Neuroprotection in Ophthalmic Neurodegenerative Diseases

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