Inflammatory Ocular Diseases and Sphingolipid Signaling

Grambergs, Richard C.; Mondal, Kalyani; Mandal, Nawajes A.

doi:10.1007/978-3-030-21162-2_8

Cited by 11 publications

(6 citation statements)

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“…This amplified sphingolipid rheostat has been confirmed to be involved not only in normal cell physiology but also in numerous pathologies (15,(45)(46)(47)(48)(49). Cumulative evidence supports its participation in diseases affecting the retina (10)(11)(12)50), thus providing new clues in the quest for innovative treatments for these pathologies.…”

Section: The Sphingolipid Rheostat: At the Crossroads Between Cellulamentioning

confidence: 86%

“…choroid)(10). Common symptoms of anterior uveitis include pain, erythema, and photophobia, while intermediate and posterior uveitis results in visual deficits(50) leading to loss of vision of approximately 30,000 people annually in the United States(215). The inflammation resulting in uveitis can arise from a number of diseases ranging from a viral infection to ocular trauma and systemic disease(216).…”

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confidence: 99%

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Sphingolipids as critical players in retinal physiology and pathology

Simón

Basu

Qaladize

et al. 2021

Journal of Lipid Research

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Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

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Section: The Sphingolipid Rheostat: At the Crossroads Between Cellulamentioning

confidence: 86%

mentioning

confidence: 99%

Sphingolipids as critical players in retinal physiology and pathology

Simón

Basu

Qaladize

et al. 2021

Journal of Lipid Research

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“…A study has indicated that HIF-1 expression in hypoxic conditions in glaucoma might be a crucial stage in damage to optic nerve axon and retinal ganglion cells [ 28 ]. Inflammation might be involved in the pathogenesis of glaucoma, and the sphingolipids signaling pathway plays an important signaling role in the pathophysiology of ocular inflammatory diseases [ 29 ]. Neurotrophins as a therapeutic drug for glaucoma and neurotrophin signaling pathway have been verified as vital signaling to protect the optic nerve [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Molecular Mechanism of Qing Guang An Granule in Treating Glaucoma Using Network Pharmacology and Molecular Docking

Chen

Song

Zhou

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Qing Guang An Granule (QGAG), a Chinese patent medicine, has been used clinically to treat glaucoma for more than 20 years. Objective. To explore the possible mechanism of treatment of QGAG in glaucoma by using network pharmacology and molecular docking in this study. Methods. Active compounds and targets of each herb in QGAG were retrieved via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Glaucoma-related targets were acquired from OMIM and DisGeNET database. Key targets of QGAG against glaucoma were acquired by overlapping the above targets via the Venn diagram. Using the DAVID, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the key targets were performed. The docking process was performed using the AutoDock 4.2.6 and AutoDock Vina 1.1.2. Results. The 55 active compounds and 173 targets were obtained and constructed a compound-target network. The 20 key targets of QGAG in treating glaucoma were acquired, and these targets are involved in the apoptotic process, cellular response to hypoxia, negative regulation of cell growth, and ovarian follicle development. The main pathways are p53, HIF-1, PI3K-Akt, and neurotrophin signaling pathway. Conclusion. QGAG may exert a protective effect by acting on the optic nerve at a molecular and systemic level. This study can provide a certain basis for future researches on exploring the QGAG in treating glaucoma and provide new ideas for developing new drugs.

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“…Sphingolipids (SPLs) are a diverse and ubiquitous family of lipids that function as structural components of the cellular membranes and have signaling roles in various cellular processes, including cell growth, cell adhesion, inflammation, and apoptosis [1][2][3][4]. Biochemically, all SPLs contain an amino-alcohol backbone and a covalently bound fatty acid forming the base structure of an SPL, the Ceramide (Cer).…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Profiling of Cellular Sphingolipids in Mammalian Endothelial and Microglial Cells Cultured in Normal and High-Glucose Conditions

Mondal

Grambergs

Gangaraju

et al. 2022

Cells

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Sphingolipids (SPLs) play a diverse role in maintaining cellular homeostasis. Dysregulated SPL metabolism is associated with pathological changes in stressed and diseased cells. This study investigates differences in SPL metabolism between cultured human primary retinal endothelial (HREC) and murine microglial cells (BV2) in normal conditions (normal glucose, NG, 5 mM) and under high-glucose (HG, 25 mM)-induced stress by sphingolipidomics, immunohistochemistry, biochemical, and molecular assays. Measurable differences were observed in SPL profiles between HREC and BV2 cells. High-glucose treatment caused a >2.5-fold increase in the levels of Lactosyl-ceramide (LacCer) in HREC, but in BV2 cells, it induced Hexosyl-Ceramides (HexCer) by threefold and a significant increase in Sphingosine-1-phosphate (S1P) compared to NG. Altered SPL profiles coincided with changes in transcript levels of inflammatory and vascular permeability mediators in HREC and inflammatory mediators in BV2 cells. Differences in SPL profiles and differential responses to HG stress between endothelial and microglial cells suggest that SPL metabolism and signaling differ in mammalian cell types and, therefore, their pathological association with those cell types.

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Inflammatory Ocular Diseases and Sphingolipid Signaling

Cited by 11 publications

References 113 publications

Sphingolipids as critical players in retinal physiology and pathology

Sphingolipids as critical players in retinal physiology and pathology

Exploring the Molecular Mechanism of Qing Guang An Granule in Treating Glaucoma Using Network Pharmacology and Molecular Docking

A Comprehensive Profiling of Cellular Sphingolipids in Mammalian Endothelial and Microglial Cells Cultured in Normal and High-Glucose Conditions

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