Exploring the Potential of Wild Olive (Acebuche) Oil as a Pharm‐Food to Prevent Ocular Hypertension and Fibrotic Events in the Retina of Hypertensive Mice

Abstract

ScopeOur laboratory has previously described the antioxidant and anti‐inflammatory potential of a wild olive (acebuche, ACE) oil against hypertension‐associated vascular retinopathies. The current study aims to analyze the antifibrotic effect of ACE oil on the retina of hypertensive mice.Methods and resultsMice are rendered hypertensive by administration of NG‐nitro‐L‐arginine‐methyl‐ester (L‐NAME) and simultaneously subjected to dietary supplementation with ACE oil or a reference extra virgin olive oil (EVOO). Intraocular pressure (IOP) is measured by rebound tonometry, and retinal vasculature/layers are analyzed by fundus fluorescein angiography and optical coherence tomography. Different fibrosis‐related parameters are analyzed in the retina and choroid of normotensive and hypertensive mice with or without oil supplementation. Besides preventing the alterations found in hypertensive animals, including increased IOP, reduced fluorescein signal, and altered retinal layer thickness, the ACE oil‐enriched diet improves collagen metabolism by regulating the expression of major fibrotic process modulators (matrix metalloproteinases, tissue inhibitors of metalloproteinases, connective tissue growth factor, and transforming growth factor beta family).ConclusionRegular consumption of EVOO and ACE oil (with better outcomes in the latter) might help reduce abnormally high IOP values in the context of hypertension‐related retinal damage, with significant reduction in the surrounding fibrotic process.

The Anti-Inflammatory and Antioxidant Properties of Acebuche Oil Exert a Retinoprotective Effect in a Murine Model of High-Tension Glaucoma

“…The ameliorative effects exerted on the glaucomatous retina by an ACE oil-enriched diet do not appear to rely on IOP reduction in the MCE model; similar results were previously obtained in rodent glaucoma models treated with other nutraceutical compounds [32,46,53,95]. Nevertheless, Santana-Garrido et al recently described the ability of ACE oil-enriched diet to restore IOP levels in Nω-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive mice [28]. L-NAME is able to inhibit nitric oxide synthases, particularly reducing endothelial nitric oxide production and thus inducing systemic vasoconstriction [96].…”

“…Indeed, ACE oil shows a higher quantity of sterols, tocopherols (e.g., vitamin E) and triterpene acids compared to the classic extra-virgin olive oil [26,89]. In this respect, a recently published work showed that in a mouse model of glaucoma ACE oil have better retinoprotective activity than a reference extra-virgin olive oil in terms of antioxidant, anti-inflammatory and antifibrotic effects, suggesting that the peculiar composition of ACE oil may be responsible for its improved features [28]. Among these components, vitamin E is a powerful fat-soluble antioxidant that is able to prevent the oxidation of polyunsaturated fatty acids in cell membranes.…”

“…A commercial rodent chow (ROD14IRR, Sodispan Research, Altromin, Germany) was crushed in powder form and then homogeneously mixed with ACE oil to reach a final concentration of 12% (w/w) of this oil in accordance with previous literature [26][27][28]. The so-prepared oil-powder pellets were maintained at 4 • C in the dark until daily usage.…”

“…Due to the well-demonstrated beneficial properties of ACE oil [26][27][28], we investigated the potential anti-inflammatory effect of an ACE oil-enriched diet in the MCE glaucoma model. The results reported in Figure 4A-D show that the mRNA and protein expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) were drastically increased in the MCE model, while the ACE oil-enriched diet prevented this upregulation, restoring a control-like situation in both IL-6 and TNFα mRNA and protein expression.…”

“…ACE olive tree is one of the oldest trees worldwide [24] and the oil derived from it contains tocopherols (e.g., vitamin E), sterols, triterpene acids and secoiridoid compounds in higher quantity compared to the classic extra virgin olive oil [25]. Moreover, it was recently demonstrated that ACE oil-enriched diet exerts anti-inflammatory, antioxidant and retinoprotective effects in a mouse model of arterial hypertension [26][27][28]. It is worth noting that ACE oil is safe and well tolerated, and no adverse effects have been reported thus far.…”