Palmitoylethanolamide (PEA) is a lipid mediator naturally synthesized in the body during inflammation and tissue damage; it is endowed with neuroprotective, anti-neuroinflammatory, and analgesic properties .
PEA was isolated from tissues, body fluids, and purified lipid fractions of egg yolk, soybeans, and peanut meal, and it has been found in a wide variety of food .
At a dosage of 600/1200 mg/day, PEA is marketed as a medical food in several European countries, and it is used as a dietary supplement in ocular diseases in Italy .
Its use as a dietary supplement in glaucoma was validated by multiple clinical studies.
Meanwhile, preclinical studies have investigated its mechanism of action highlighting an entourage effect with the endocannabinoid system . This system includes the endogenous ligands anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which are the enzymes responsible for their synthesis and degradation, such as fatty acid amide hydrolase (FAAH), MGL, and the cannabinoid type-1 (CB1) and type-2 (CB2) receptors .
Early evidence indicates that the levels of PEA and 2-AG decreased significantly in eye tissues of glaucomatous patients as compared to normal donors , suggesting that the lipid mediators PEA and 2-AG have a role in this ocular disease.
Patients with ocular disease showed protective effects after an intake of PEA as documented in clinical trials.
Oral intake of PEA (600 mg/day) for fifteen days prevented the significant increase of postoperative IOP in patients who had undergone bilateral laser iridotomy as compared to those pretreated with placebo .
After three months of PEA oral intake, a reduction of IOP and a significantly improved endothelial function were observed in ocular hypertension (OHT) patients as compared to placebo-treated. Interestingly, this effect lasted longer than the period of PEA administration .
A significant reduction of IOP values was observed in POAG and OH patients after oral administration of PEA for two months .
In NTG patients, Costagliola and colleagues (2014) demonstrated that the systemic administration of PEA for six months reduced IOP and improved visual field indices; no ocular or systemic side effects were recorded after this longer lasting treatment .
Recently, Rossi and colleagues (2020) demonstrated that the oral administration of PEA (600 mg/day) for four months enhanced the electrical activity of RGCs and retina, which was measured by pattern evoked electroretinograms (PERG), and improved IOP .
These clinical data, together with preclinical results, indicate that PEA has multiple potential beneficial effects in patients with glaucoma :
increase of aqueous humor outflow through the GPR55 and the PPARα receptors and the involvement of the p42/44 mitogen-activated protein kinase (MAPK) pathway ;
vasorelaxation of the ophthalmic artery by acting on the transcription factors PPARα ;
engagement of the cannabinoid system, which has been shown to mediate neuroprotective effects in both the central nervous system  and eye . In a rat model of ischemia reperfusion injury, AEA reduced glutamate excitotoxicity and prevented apoptosis by activating CB1 and TRPV1 receptors [128,129,130]. An interesting hypothesis is that PEA could compete with AEA for the FAAH active site, increasing AEA concentration and its neuroprotective effects .
a fourth beneficial effect of PEA is reduced neuroinflammation mediated by mast cell modulation to counteract the hyperactivated glial cells typically found in glaucoma. [added by FitEyes editor]
NOTE: emphasis added in text above. Minor edits made to improve readability for a general audience. And the 4th item was added to the list based on other research studies.
- Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma - PMC
- Nutrients. 2020 Oct 16;12(10):3158.
- Free PMC article
- PMID: 33081127
- PMCID: PMC7602834
- DOI: 10.3390/nu12103158