Palmitoylethanolamide, a Natural Retinoprotectant: Its Putative Relevance for the Treatment of Glaucoma and Diabetic Retinopathy

Table 1

Summary of preclinical studies related to PEA’s cytoprotective effects.

Year	Dose PEA	Main results	Reference
2015	5 μM in vitro	Inhibition of the Ca^2+-dependent release of glutamate	[24]
2015	5 mg/kg	Diminished inflammation, demyelination, axonal damage, and inflammatory cytokine expression in a multiple sclerosis model	[25]
2015	0.1 μM in vitro	Protection cell viability in cultured cortical neurons and astrocytes against inflammation	[26]
2015	10^−8–10^−6 M	Concentration-dependently reduced expression of proinflammatory and proangiogenic markers	[27]
2014	1 mg/kg	Prevention of induced afferent mechanical sensitization	[28]
2014	200, 400 and 800 µg/mL	Inhibition of inflammation markers and chymase expression in granulomatous tissue	[29]
2014	30 mg/kg sc	Increased AMP-activated protein kinase-α phosphorylation and carnitine palmitoyltransferase 1 transcription in adipose tissue; polarized adipose tissue macrophages to M2 lean phenotype	[30]
2014	10 mg/kg	Reduction of structural radiation injury, intestinal wall thickness, collagen deposition, intestinal inflammation, and increased anti-inflammatory IL-10 and IL-6	[31]
2013	10 mg/kg	Reduction of the clinical signs of type II collagen-induced arthritis as well as of paw edema compared to control	[32]
2013	2, 10 or 50 mg/kg	Improves all macroscopic signs of colitis and decreases the expression and release of all the proinflammatory markers	[33]
2013	30 mg/kg	Reduction of hypertension and protects kidney injury	[34]
2013	1 μM control in vivo	Protected SCI-associated neuroinflammation in vivo and in vitro	[35]
2013	0.1 µM, in vitro	Rescue of neuron damage by amyloid and reduction of neuroinflammation (decrease of astrocyte activation)	[36]
2013	5–10 mg/kg	Normalizing the activity of sensitized nociceptive neurons; significant reduction of mechanical allodynia and thermal hyperalgesia in a dose-dependent manner	[37]
2013	10 mg/kg	Strong reduction of microglia activation and PEA delayed mast cell recruitment, protection of mast cells against degranulation, and abolition of the nerve growth factor increase, reducing pain	[38]
2013	10 mg/kg	Protection of spinal cord damage; restoration of PPAR-δ and PPAR-γ expression in spinal cord after damage	[39]
2013	10, 20, 40, 60 mg/kg i.p.	Showing anti-epileptic properties in a rat model	[40]
2013	NR	Blunted Aβ1-42-induced neurotoxicity and controlled glial activation	[41]
2012	10 mg/kg	Significant attenuation of the degree of renal dysfunction, injury, and inflammation caused by ischemia-reperfusion injury	[42]
2012	10 mg/kg	Reduction of MPTP-induced microglial activation, the number of GFAP-positive astrocytes, and reduction of neutrophil infiltrations, reduction of TNF-, IL-1 and iNOS in spinal cord and prevention of SCI-induced IB-α degradation and Bax expression	[43]
2012	10 mg/kg	Reduction of apoptosis, brain infarctions, and various inflammatory parameters	[44]
2011	10 mg/kg	Significant reduction of mast cell infiltration, expression of mediators like NGF, the activation of microglia, and astrocytes expressing cannabinoid CB(2) receptor after spinal cord injury	[45]
2008	10 mg/kg	Significant reduction of spinal cord inflammation and tissue injury, neutrophil infiltration, and proinflammatory cytokine expression and significant amelioration of the recovery of motor limb function	[46]

NR: Nonreported.