Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis

Fox, Timothy P.; Gotlinger, Katherine; Dunn, Max S.; Lee, Olivia L; Milman, Tatyana; Zaidman, Gerald W.; Schwartzman, Michal Laniado; Bellner, Lars

doi:10.1097/ico.0b013e3182936915

Cited by 11 publications

(6 citation statements)

References 38 publications

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“…Our findings of higher PC and PS in our samples of pterygium could be explained by the increase in proliferation, angiogenesis and epithelial mesenchymal transition, which is observed in this pathology. Besides, Fox et al have demonstrated that in pterygium there is an increase of autacoid12-HETE, a powerful pro-inflammatory and pro-angiogenic mediator [49]. Our investigation shows the existence of EPCD, pinguecula and pterygium south of parallel 30, outside the "pterygium belt" described by Cameron [50].…”

Section: Discussionsupporting

confidence: 63%

Ocular surface degenerative diseases studies in an isolated region of Argentine Patagonia

Suárez¹,

Crim²,

Correa³

et al. 2019

New Front Ophthalmol

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Aim:The aim of this study was to investigate the prevalence of Environmental proteinaceous corneal degeneration (EPCD), pinguecula and pterygium and any association among them, and to perform lipidomic studies in some samples of EPCD and pterygium. Materials and methods:It was a transversal/observational and analytical study; the sample was consecutive non-probabilistic. All patients examined resided all their lives in the department El Cuy (Río Negro). Corneal epithelium and conjunctiva tissue samples were taken to perform mass spectrometric lipidomic studies.Results: One hundred and fifty-nine patients were studied (52.83% male and 47.17% female). The prevalence of ophthalmoheliosis was: pinguecula 32.1%, EPCD 28.9%, and pterygium 13.2%. A statistically significant association was found between EPCD and male patients (21.4% vs 7.5%) (p <0.05). There was association between EPCD with pinguecula and with pterygium, both more frequent in males (p <0.05). Lipidomic studies in EPCD showed a decrease in the concentration of phospholipids in affected areas (15 times less). In pterygium, there was an increase in the concentration of phospholipids (6.67 times more). Conclusion:Our investigation shows important prevalence of EPCD, pinguecula and pterygium in individuals that live at El Cuy (Argentine Patagonia). As far as we know, this is the first work in the world that shows coexistences between these three ophthalmoheliosis. The decrease concentration of phospholipids in EPCD affected areas could be due to lipid peroxidation, as a consequence of oxidative stress. On the other hand, higher levels of PC and PS in pterygium samples could be explained by the increase in proliferation and angiogenesis.

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Section: Discussionsupporting

confidence: 63%

Ocular surface degenerative diseases studies in an isolated region of Argentine Patagonia

Suárez¹,

Crim²,

Correa³

et al. 2019

New Front Ophthalmol

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“…Reactions were terminated by adding 2 volume of HPLC grade methanol and stored at −80C prior to analysis to each sample. The generated eicosanoid profiles were determined by LC-MS-MS, as previously described [44] .…”

Section: Methodsmentioning

confidence: 99%

Deletion of the Murine Cytochrome P450 Cyp2j Locus by Fused BAC-Mediated Recombination Identifies a Role for Cyp2j in the Pulmonary Vascular Response to Hypoxia

Zhou

Beloiartsev

et al. 2013

PLoS Genet

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Epoxyeicosatrienoic acids (EETs) confer vasoactive and cardioprotective functions. Genetic analysis of the contributions of these short-lived mediators to pathophysiology has been confounded to date by the allelic expansion in rodents of the portion of the genome syntenic to human CYP2J2, a gene encoding one of the principle cytochrome P450 epoxygenases responsible for the formation of EETs in humans. Mice have eight potentially functional genes that could direct the synthesis of epoxygenases with properties similar to those of CYP2J2. As an initial step towards understanding the role of the murine Cyp2j locus, we have created mice bearing a 626-kb deletion spanning the entire region syntenic to CYP2J2, using a combination of homologous and site-directed recombination strategies. A mouse strain in which the locus deletion was complemented by transgenic delivery of BAC sequences encoding human CYP2J2 was also created. Systemic and pulmonary hemodynamic measurements did not differ in wild-type, null, and complemented mice at baseline. However, hypoxic pulmonary vasoconstriction (HPV) during left mainstem bronchus occlusion was impaired and associated with reduced systemic oxygenation in null mice, but not in null mice bearing the human transgene. Administration of an epoxygenase inhibitor to wild-type mice also impaired HPV. These findings demonstrate that Cyp2j gene products regulate the pulmonary vascular response to hypoxia.

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“…Hemeoxygenases (HOs) have been shown to regulate the levels of eicosanoids derived in the cyclooxygenase, lipoxygenase, and cytochrome P450 monooxygenase (CYP) pathways. Up regulation of HO-1 or increased HO activity can suppress PGE 2 , inducing production of 15-hydroxyeicosatetraenoic acid (HETE), lipoxins, and resolvins (Abraham and Kappas, 2008; Fox et al, 2013). In mammalian cells, sciadonic acid cannot be directly metabolized to PGE 2 , but it can compete with AA for incorporation into phospholipids and lead to a reduction in PGE 2 production (Ells et al, 2012).…”

Section: Othersmentioning

confidence: 99%

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

Liu

Wang

et al. 2016

Front. Microbiol.

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Candida is an important opportunistic fungal pathogen, especially in biofilm associated infections. The formation of a Candida biofilm can decrease Candida sensitivity to antifungal drugs and cause drug resistance. Although many effective antifungal drugs are available, their applications are limited due to their high toxicity and cost. Seeking new antifungal agents that are effective against biofilm-associated infection is an urgent need. Many research efforts are underway, and some progress has been made in this field. It has been shown that the arachidonic acid cascade plays an important role in fungal morphogenesis and pathogenicity. Notably, prostaglandin E2 (PGE2) can promote the formation of a Candida biofilm. Recently, the inhibition of PGE2 has received much attention. Studies have shown that cyclooxygenase (COX) inhibitors, such as aspirin, ibuprofen, and indomethacin, combined with fluconazole can significantly reduce Candida adhesion and biofilm development and increase fluconazole susceptibility; the MIC of fluconazole can be decrease from 64 to 2 μg/ml when used in combination with ibuprofen. In addition, in vivo studies have also confirmed the antifungal activities of these inhibitors. In this article, we mainly review the relationship between PGE2 and Candida biofilm, summarize the antifungal activities of COX inhibitors and analyze the possible antifungal activity of microsomal prostaglandin E synthase-1 (MPGES-1) inhibitors; additionally, other factors that influence PGE2 production are also discussed. Hopefully this review can disclose potential antifungal targets based on the arachidonic acid cascade and provide a prevailing strategy to alleviate Candida albicans biofilm formation.

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Dysregulated Heme Oxygenase–Ferritin System in Pterygium Pathogenesis

Cited by 11 publications

References 38 publications

Ocular surface degenerative diseases studies in an isolated region of Argentine Patagonia

Ocular surface degenerative diseases studies in an isolated region of Argentine Patagonia

Deletion of the Murine Cytochrome P450 Cyp2j Locus by Fused BAC-Mediated Recombination Identifies a Role for Cyp2j in the Pulmonary Vascular Response to Hypoxia

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

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