Analyses of pseudoexfoliation aqueous humor lipidome

Collao, Vanessa; Morris, Jada; Chauhan, Muhammad Z.; Abdelrahman, Leila; Martínez-de-la-Casa, J.M.; Vidal‐Villegas, Beatriz; Burgos-Blasco, Bárbara; Bhattacharya, Sanjoy K.

doi:10.1039/d1mo00495f

Cited by 2 publications

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“…These results revealed the importance of lipid metabolism equilibrium between blood endothelial cells and surrounding cells, for example corneal epithelium or keratocyte. Normal aqueous humor has been shown to contain more than 400 lipid species (Jahn et al, 1983;Collao et al, 2022;Liu et al, 2022), and the corneal endothelial cells serves as a dynamic barrier that separates aqueous humor from corneal stroma (Hasan and Fischer, 2021). It has been widely reported that increased intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) diets reduce choroidal neovascularization in mice (Gong et al, 2016a;Gong et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway

et al. 2022

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Purpose: The purpose of this study was to explore the potential underlying mechanism of anti-vascular effects of peroxisome proliferator–activated receptor α (PPARα) agonist fenofibrate against corneal neovascularization (CNV) through the changes of lipid metabolism during CNV.Methods: A suture-induced CNV model was established and the clinical indications were evaluated from day 1 to day 7. Treatments of vehicle and fenofibrate were performed for 5 days after suture and the CNV areas were compared among the groups. The eyeballs were collected for histological analysis, malondialdehyde (MDA) measurement, terminal deoxynucleotidyl transferase 2′-deoxyuridine 5′-triphosphate nick end labeling (TUNEL) staining, western blot, quantitative real-time PCR (qRT-PCR) assays and immunohistochemical (IHC) staining to elucidate pathological changes and the underlying mechanism.Results: Lipi-Green staining and MDA measurement showed that lipid deposition and peroxidation were increased in the CNV cornea while the expression of long-chain acyl-coenzyme A synthetase 1 (ACSL1), carnitine palmitoyltransterase 1A(CPT1A) and medium-chain acyl-coenzyme A dehydrogenase (ACADM), which are key enzymes of fatty acid β-oxidation (FAO) and targeted genes of peroxisome proliferator-activated receptor alpha (PPARα) pathway, were decreased in CNV cornea. Fenofibrate suppressed lipid accumulation and peroxidation damage in the CNV cornea. Fenofibrate upregulated the expression levels of PPARα, ACSL1, CPT1A, and ACADM compared with vehicle group. IHC staining indicated that fenofibrate also decreased the expression of VEGFa, VEGFc, TNFα, IL1β and CD68.Conclusion: Disorder of lipid metabolism may be involved in the formation of suture-induced CNV and fenofibrate played anti-neovascularization and anti-inflammatory roles on cornea by regulating the key enzymes of lipid metabolism and ameliorating lipid peroxidation damage of cornea through PPARα signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway

et al. 2022

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“…Apolipoproteins are a group of key proteins participating in lipid metabolism and transport in the body. Apolipoproteins have been found to be part of the PEXM, especially in the pupillary area of the anterior lens capsule (Collao et al, 2022; Morris et al, 2021; Ronci et al, 2013). The APOE E2 allele was significantly linked to PEX development (Yilmaz et al, 2005).…”

Section: Pseudoexfoliative Glaucomamentioning

confidence: 99%

Secondary glaucoma: Toward interventions based on molecular underpinnings

Mueller,

Lam,

Kishor

et al. 2023

WIREs Mechanisms of Disease

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Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying condition. Pseudoexfoliation and pigment dispersion syndromes are common causes of secondary glaucoma. Their respective deposits may obstruct the trabecular meshwork, leading to aqueous humor outflow resistance, ocular hypertension, and optic neuropathy. There are no disease‐specific interventions available for either. Pseudoexfoliation syndrome is characterized by fibrillar deposits (pseudoexfoliative material) on anterior segment structures. Over a decade of multiomics analyses taken together with the current knowledge on pseudoexfoliative glaucoma warrant a re‐think of mechanistic possibilities. We propose that the presence of nucleation centers (e.g., vitamin D binding protein), crosslinking enzymes (e.g., transglutaminase 2), aberrant extracellular matrix, flawed endocytosis, and abnormal aqueous‐blood barrier contribute to the formation of proteolytically resistant pseudoexfoliative material. Pigment dispersion syndrome is characterized by abnormal iridolenticular contact that disrupts iris pigment epithelium and liberates melanin granules. Iris melanogenesis is aberrant in this condition. Cytotoxic melanogenesis intermediates leak out of melanosomes and cause iris melanocyte and pigment epithelium cell death. Targeting melanogenesis can likely decrease the risk of pigmentary glaucoma. Skin and melanoma research provides insights into potential therapeutics. We propose that specific prostanoid agonists and fenofibrates may reduce melanogenesis by inhibiting cholesterol internalization and de novo synthesis. Additionally, melatonin is a potent melanogenesis suppressor, antioxidant, and hypotensive agent, rendering it a valuable agent for pigmentary glaucoma. In pseudoexfoliative glaucoma, where environmental insults drive pseudoexfoliative material formation, melatonin's antioxidant and hypotensive properties may offer adjunct therapeutic benefits.This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology

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Analyses of pseudoexfoliation aqueous humor lipidome

Abstract: Pseudoexfoliation syndrome (PEX) is a systemic disorder that manifests as fluffy, proteinaceous fibrillar material throughout the body. In the eye such deposits result in glaucoma (PEXG), due to impeding aqueous...

Cited by 2 publications

References 39 publications

Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway

Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway

Secondary glaucoma: Toward interventions based on molecular underpinnings

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