PPARα-Dependent Effects of Palmitoylethanolamide Against Retinal Neovascularization and Fibrosis

Ye, Sihao; Chen, Qian; Jiang, Nan; Xu, Liang; Li, Jingming; Zong, Rongrong; Huang, Caihong; Qiu, Yan; Ma, Jian-Xing; Liu, Zuguo

doi:10.1167/iovs.61.4.15

Cited by 13 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PPAR expression and activation provides clear beneficial effects on different retinopathies of vascular origin [ 58 ]. These pleiotropic effects have prompted the use of different PPAR agonists to treat various inflammatory retinopathies, including DR, oxygen-induced retinopathy and AMD [ 59 , 60 , 61 ]. In this regard, PPARs have been shown to downregulate the expression of pro-inflammatory biomarkers in retinopathy microvascular dysfunction, as well as to regulate endothelial cell function by targeting angiogenesis [ 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Action of Dietary Wild Olive (Acebuche) Oil in the Retina of Hypertensive Mice

Santana-Garrido

Reyes-Goya

Milla-Navarro

et al. 2021

Foods

View full text Add to dashboard Cite

Inflammation plays a crucial role in the course of eye diseases, including many vascular retinopathies. Although olive oil is known to have beneficial effects against inflammatory processes, there is no information available on the anti-inflammatory potential of the wild olive tree (namely, acebuche (ACE) for the primitive Spanish lineages). Here we investigate the anti-inflammatory effects of ACE oil in the retina of a mouse model of arterial hypertension, which was experimentally induced by administration of L-NAME (NG-nitro-L-arginine-methyl-ester). The animals were fed supplements of ACE oil or extra virgin olive oil (EVOO, for comparative purposes). Retinal function was assessed by electroretinography (ERG), and different inflammation-related parameters were measured in the retina and choroid. Besides significant prevention of retinal dysfunction shown in ERG recordings, ACE oil-enriched diet upregulated the expression of the anti-inflammatory markers PPARγ, PPARα and IL-10, while reducing that of major proinflammatory biomarkers, IL-1β, IL-6, TNF-α and COX-2. This is the first report to highlight the anti-inflammatory properties of an ACE oil-enriched diet against hypertension-related retinal damage. Noteworthy, dietary supplementation with ACE oil yielded better results compared to a reference EVOO.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Action of Dietary Wild Olive (Acebuche) Oil in the Retina of Hypertensive Mice

Santana-Garrido

Reyes-Goya

Milla-Navarro

et al. 2021

Foods

View full text Add to dashboard Cite

show abstract

“…However, an example will suffice to illustrate the multitude of downstream effects of PEA. Ye et al [73] investigated the effects of PEA in a mouse model of oxygen-induced retinopathy, whereby mice were exposed to 75% oxygen for 5 days on post-natal days 7 to 12, after which time they were returned to a normoxic environment and treated with PEA for 5-15 days depending upon the experiment. The PEA treatment reduced levels at protein and mRNA levels of the angiogenic marker vascular endothelial growth factor (VEGF) and the inflammatory cytokine TNF-α, the number of TUNEL-positive cells, the avascular area as well as markers of extracellular matrix, profibrotic changes, and gliosis [73].…”

Section: Downstream Effects Of Peamentioning

confidence: 99%

The Basal Pharmacology of Palmitoylethanolamide

Rankin

Fowler

2020

IJMS

View full text Add to dashboard Cite

Palmitoylethanolamide (PEA, N-hexadecanoylethanolamide) is an endogenous compound belonging to the family of N-acylethanolamines. PEA has anti-inflammatory and analgesic properties and is very well tolerated in humans. In the present article, the basal pharmacology of PEA is reviewed. In terms of its pharmacokinetic properties, most work has been undertaken upon designing formulations for its absorption and upon characterising the enzymes involved in its metabolism, but little is known about its bioavailability, tissue distribution, and excretion pathways. PEA exerts most of its biological effects in the body secondary to the activation of peroxisome proliferator-activated receptor-α (PPAR-α), but PPAR-α-independent pathways involving other receptors (Transient Receptor Potential Vanilloid 1 (TRPV1), GPR55) have also been identified. Given the potential clinical utility of PEA, not least for the treatment of pain where there is a clear need for new well-tolerated drugs, we conclude that the gaps in our knowledge, in particular those relating to the pharmacokinetic properties of the compound, need to be filled.

show abstract

“…Pharmacological PPARα activation by palmitoylethanolamide (PEA) reduced retinal neovascularization and fibrotic changes and suppressed glial activation in proliferative retinopathy and neovascular age-related macular degeneration mouse models [ 102 ]. In cardiovascular studies, PEA exerted direct vaso-relaxation of the bovine ophthalmic artery through the PPARα transcription factors, suggesting a function of PPARα on physiological vascular regulation [ 103 ].…”

Section: Functions Of Pparα In the Eyementioning

confidence: 99%

PPARα Agonist Oral Therapy in Diabetic Retinopathy

2020

View full text Add to dashboard Cite

Diabetic retinopathy (DR) is an eye condition that develops after chronically poorly-managed diabetes, and is presently the main cause for blindness on a global scale. Current treatments for DR such as laser photocoagulation, topical injection of corticosteroids, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and vitreoretinal surgery are only applicable at the late stages of DR and there are possibilities of significant adverse effects. Moreover, the forms of treatment available for DR are highly invasive to the eyes. Safer and more effective pharmacological treatments are required for DR treatment, in particular at an early stage. In this review, we cover recently investigated promising oral pharmacotherapies, the methods of which are safer, easier to use, patient-friendly and pain-free, in clinical studies. We especially focus on peroxisome proliferator-activator receptor alpha (PPARα) agonists in which experimental evidence suggests PPARα activation may be closely related to the attenuation of vascular damages, including lipid-induced toxicity, inflammation, an excess of free radical generation, endothelial dysfunction and angiogenesis. Furthermore, oral administration of selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) agonists may induce hepatic fibroblast growth factor 21 expression, indirectly resulting in retinal protection in animal studies. Our review will enable more comprehensive approaches for understanding protective roles of PPARα for the prevention of DR development.

show abstract

PPARα-Dependent Effects of Palmitoylethanolamide Against Retinal Neovascularization and Fibrosis

Cited by 13 publications

References 46 publications

Anti-Inflammatory Action of Dietary Wild Olive (Acebuche) Oil in the Retina of Hypertensive Mice

Anti-Inflammatory Action of Dietary Wild Olive (Acebuche) Oil in the Retina of Hypertensive Mice

The Basal Pharmacology of Palmitoylethanolamide

PPARα Agonist Oral Therapy in Diabetic Retinopathy

Contact Info

Product

Resources

About