Platelet activating factor in the eye: Physiological roles, diseases and future perspectives

Dalmaso, Barbara; Silva, Ildefonso; Fragel-Madeira, Lucianne; Jancar, Sônia; Debbio, Carolina Beltrame Del

doi:10.1016/j.prostaglandins.2020.106522

Cited by 8 publications

(4 citation statements)

References 152 publications

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“…While the precise roles of PAF/PAFR in retinal progenitor/stem cell maintenance and cell fate determination are being elucidated, their involvement in several retinal pathologies has already been described in the literature [ 44 , 45 ]. A recent review on the involvement of PAF/PAFR in ocular pathologies was published by our group.…”

Section: Discussionmentioning

confidence: 99%

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

Dalmaso,

Silva-Junior,

Jancar

et al. 2024

IJMS

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The retina is a central nervous tissue essential to visual perception and highly susceptible to environmental damage. Lower vertebrate retinas activate intrinsic regeneration mechanisms in response to retinal injury regulated by a specialized population of progenitor cells. The mammalian retina does not have populations of progenitor/stem cells available to activate regeneration, but contains a subpopulation of differentiated cells that can be reprogrammed into retinal stem cells, the ciliary epithelium (CE) cells. Despite the regenerative potential, stem cells derived from CE exhibit limited reprogramming capacity probably associated with the expression of intrinsic regulatory mechanisms. Platelet-activating factor (PAF) is a lipid mediator widely expressed in many cells and plays an important role in stem cell proliferation and differentiation. During mammalian development, PAF receptor signaling showed important effects on retinal progenitors’ cell cycle regulation and neuronal differentiation that need to be further investigated. In this study, our findings suggested a dynamic role for PAF receptor signaling in CE cells, impacting stem cell characteristics and neurosphere formation. We showed that PAF receptors and PAF-related enzymes are downregulated in retinal progenitor/stem cells derived from PE cells. Blocking PAFR activity using antagonists increased the expression of specific progenitor markers, revealing potential implications for retinal tissue development and maintenance.

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Section: Discussionmentioning

confidence: 99%

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

Dalmaso,

Silva-Junior,

Jancar

et al. 2024

IJMS

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“…Indeed, many different types of small molecules of diverse structures and origins (natural products and synthetic) have been discovered, characterized and validated as PAF receptor antagonists (Figures 4 and 5 and Tables 1 and 2 ). 8 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 …”

Section: Role Of Paf In Ocular Diseasesmentioning

confidence: 99%

PAF‐induced inflammatory and immuno‐allergic ophthalmic diseases and their mitigation with PAF receptor antagonists: Cell and nuclear effects

Sharif

2022

BioFactors

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Ocular allergies are becoming more prevalent as more airborne pollutants, irritants and microbes pervade our environment. Inflammatory and allergic mediators released by dendritic and mast cells within the conjunctiva cause allergic conjunctivitis (AC), a prevalent ocular surface disorder that affects >40% of the world's human population on a seasonal or perennial basis. Even though histamine is a major culprit, platelet‐activating factor (PAF) also contributes to AC, acting either directly or synergistically with histamine and other mediators. PAF receptor‐meditated inflammatory reactions, via cell‐membrane‐bound and nuclear‐membrane‐bound and nuclear PAF receptors, are also implicated in the etiology of other eye diseases such as uveitis, diabetic retinopathy, corneal and choroidal neovascularization, and age‐related macular degeneration which cause serious visual impairment and can lead to blindness. This review highlights the various deleterious elements implicated in the pathological aspects of ocular allergic reactions and inflammation and provides concepts and treatment options to mitigate these eye disorders with a special focus on PAF and PAF receptor antagonists.

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“…It activates the inflammatory cascade through G protein-coupled receptors, stimulating inflammatory cell production and releasing inflammatory mediators, such as TNF-α, IL-1 and IL-6, thereby increasing vascular permeability and leading to a vascular inflammatory response. 104 , 105 Normally, AA is bound to the cell membrane as an ester bond until PLA2 is activated through calcium signalling to hydrolyse the ester bond and release AA. AA will synthesise pro-inflammatory mediators, activate intracellular inflammatory signals, promote the synthesis and release of inflammatory factors, such as TNF and ILs, and amplify the inflammatory response.…”

Section: Paf-mediated Cytokine Involvement In Nafldmentioning

confidence: 99%

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

Yin

Shi

2022

DMSO

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Non-alcoholic fatty liver disease (NAFLD) is a multifaceted clinicopathological syndrome characterised by excessive hepatic lipid accumulation that causes steatosis, excluding alcoholic factors. Platelet-activating factor (PAF), a biologically active lipid transmitter, induces platelet activation upon binding to the PAF receptor. Recent studies have found that PAF is associated with gamma-glutamyl transferase, which is an indicator of liver disease. Moreover, PAF can stimulate hepatic lipid synthesis and cause hypertriglyceridaemia. Furthermore, the knockdown of the PAF receptor gene in the animal models of NAFLD helped reduce the inflammatory response, improve glucose homeostasis and delay the development of NAFLD. These findings suggest that PAF is associated with NAFLD development. According to reports, patients with NAFLD or animal models have marked platelet activation abnormalities, mainly manifested as enhanced platelet adhesion and aggregation and altered blood rheology. Pharmacological interventions were accompanied by remission of abnormal platelet activation and significant improvement in liver function and lipids in the animal model of NAFLD. These confirm that platelet activation may accompany a critical importance in NAFLD development and progression. However, how PAFs are involved in the NAFLD signalling pathway needs further investigation. In this paper, we review the relevant literature in recent years and discuss the role played by PAF in NAFLD development. It is important to elucidate the pathogenesis of NAFLD and to find effective interventions for treatment.

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Platelet activating factor in the eye: Physiological roles, diseases and future perspectives

Cited by 8 publications

References 152 publications

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

PAF‐induced inflammatory and immuno‐allergic ophthalmic diseases and their mitigation with PAF receptor antagonists: Cell and nuclear effects

Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease

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