Lipid Signaling in Ocular Neovascularization

Terao, Ryo; Kaneko, Hiroki

doi:10.3390/ijms21134758

Cited by 18 publications

(12 citation statements)

References 175 publications

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“…Additionally, NF-κB, an essential regulator of IL-6 and PGE2, and COX-2, whose selective antagonist inhibits subretinal fibrosis, are both further crucial regulators of CNV. [ 19 , 218 , 219 , 220 ]. Compelling evidence also suggests that ocular infiltration of a specific type of macrophages (M2 macrophage) via the LTB4-BLT1 signaling pathway is intimately involved in the development of laser-induced CNV [ 69 ].…”

Section: Pathology Of Age-related Macular Degeneration (Amd) and Imentioning

confidence: 99%

“…Lipids provide energy storage and serve as structural components of cell membranes, ensuring the homeostasis of these barriers. Lipids can also act as signaling molecules, influencing many processes, including gene expression [ 18 , 19 ]. Long-chain n-3 (also called omega-3) fatty acids are particularly essential for the normal growth and neural development of the brain and eye [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

2020

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Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and are necessary for homeostasis. They are important retinal membrane components and are involved in energy storage. n-3 fatty acids also have antioxidant and anti-inflammatory properties, and their suppressive effects against ROP, DR, and AMD have been previously evaluated. α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites have been shown to alleviate retinal oxidative stress and inflammation involving various biological signaling pathways. In this review, we summarize the current understanding of the n-3 fatty acids effects on the mechanisms of these retinal diseases and how they exert their therapeutic effects, focusing on ALA, EPA, DHA, and their metabolites. This knowledge may provide new remedial strategies for n-3 fatty acids in the prevention and treatment of retinal diseases associated with oxidative stress and inflammation.

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Section: Pathology Of Age-related Macular Degeneration (Amd) and Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

2020

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“…Indeed, our analysis of retinal imaging in MacTel patients indicated that low SM correlated with retinal neovascularization. Though no direct correlations have previously been described between neovascularization and SM, others have observed associations between ceramides and sphingosine 1-phosphate with ocular neovascularization and angiogenesis 44 . These results, combined with the reduction in glycosylated sphingolipids, further link MacTel pathogenesis to dysregulation of membrane lipids 45 .…”

Section: Discussionmentioning

confidence: 90%

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease

Green

Bonelli

Ansell

et al. 2022

Preprint

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The non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insights into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we performed a targeted metabolomic analysis of these pathways in sera from patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. In a cohort of >350 participants, MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model indicates this depletion in complex sphingolipids can be driven by low dietary serine and glycine. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. These results highlight metabolic distinctions between these two diseases, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches.

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“…In the previous study, it histologically revealed that lipid was packed underneath PED 11 . It has been considered that lipid signaling promotes the development of neovascularization in ocular tissues 12 . Given that lipid volume is associated with signal strength, it might be reasonable that PED width is associated with MNV.…”

Section: Discussionmentioning

confidence: 99%

Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment

Shijo

Sakurada

Takada

et al. 2022

Sci Rep

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To investigate the incidence and risk of advanced age-related macular degeneration (AMD), including geographic atrophy (GA) and macular neovascularization (MNV), in eyes with drusenoid pigment epithelial detachment (PED). Eighty-five eyes with drusenoid PED from 85 patients (77.2 ± 7.0 years, male/female: 44/41) were included in this study. Patients were followed up every 1–3 months via spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. If exudation was observed on SD-OCT, fluorescein and indocyanine green angiography were performed to confirm the MNV subtype accordingly. The maximum follow-up period was 60 months. During the study period, GA developed in 8 eyes while MNV also developed in 8 eyes. The Kaplan–Meier estimator revealed that the cumulative incidence for 60 months was 17.9% and 12.2% for GA and MNV, respectively. In eyes developing MNV, retinal angiomatous proliferation was the most common. Cox regression analysis revealed that baseline PED width was the only factor associated with advanced AMD. (p = 0.0026, Cox regression analysis). The 5-year cumulative incidence of advanced AMD, including GA and MNV, was approximately 30% in eyes with drusenoid PED among the Japanese elderly. A larger baseline PED width was the only risk factor for advanced AMD.

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Lipid Signaling in Ocular Neovascularization

Cited by 18 publications

References 175 publications

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease

Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment

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