The essential role of docosahexaenoic acid and its derivatives for retinal integrity

Swinkels, Daniëlle; Baes, Myriam

doi:10.1016/j.pharmthera.2023.108440

Cited by 18 publications

(6 citation statements)

References 184 publications

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“…The retina is rich in LC-PUFA and VLC-PUFA, which are mainly present in the discs of photoreceptor outer segments [162].…”

Section: Retinal Lc-pufa and Vlc-pufa: Physiological Rolementioning

confidence: 99%

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Brito,

Sorbier,

Mignet

et al. 2024

IJMS

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Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.

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“…The retina is rich in LC-PUFA and VLC-PUFA, which are mainly present in the discs of photoreceptor outer segments [162].…”

Section: Retinal Lc-pufa and Vlc-pufa: Physiological Rolementioning

confidence: 99%

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Brito,

Sorbier,

Mignet

et al. 2024

IJMS

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“…Therefore, new pharmacological therapies are currently needed to mitigate the pro-inflammatory environment typically induced after subretinal administration of gene therapy, contributing to the prolonged survival of photoreceptors. Among the various pharmacotherapies available, some studies have emphasized the protective effects of natural polyphenols in slowing down the degeneration of cones in individuals with RP [53][54][55].…”

Section: Introductionmentioning

confidence: 99%

Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice

Moshtaghion,

Caballano-Infantes,

Plaza Reyes

et al. 2024

Antioxidants

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Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against H2O2 oxidative stress and in rd10 mice. PIC-OCT possesses a better ADME profile than RSV. In response to H2O2, 661W cells pretreated with PIC-OCT preserved cell viability in more than 38% of cells by significantly promoting SIRT1 nuclear translocation, preserving NAD+/NADH ratio, and suppressing intracellular ROS formation. These effects result from expressing antioxidant genes, maintaining mitochondrial function, reducing PARP1 nuclear expression, and preventing AIF nuclear translocation. In rd10 mice, PIC-OCT inhibited PAR-polymer formation, increased SIRT1 expression, significantly reduced TUNEL-positive cells in the retinal outer nuclear layer, preserved ERGs, and enhanced light chamber activity (all p values < 0.05). Our findings corroborate that PIC-OCT protects photoreceptors by modulating the SIRT1/PARP1 axis in models of retinal degeneration.

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“…Docosahexaenoic acid (DHA) is a long-chain Omega-3 fatty acid that can be obtained from marine organisms [ 17 ]. DHA functions as a potent antioxidant and plays a crucial role in neural tissues such as the brain and retina [ 18 ]. Multiple clinical studies have demonstrated that oral supplementation of DHA can significantly improve the oxidative stress state in the blood [ 19 ], alleviate age-related ocular diseases [ 20 ], and provide various benefits, including neuroprotection [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic Acid Coordinating with Sodium Selenite Promotes Paraptosis in Colorectal Cancer Cells by Disrupting the Redox Homeostasis and Activating the MAPK Pathway

Zhao,

Meng,

Cai

et al. 2024

Nutrients

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Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment.

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The essential role of docosahexaenoic acid and its derivatives for retinal integrity

Cited by 18 publications

References 184 publications

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review

Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice

Docosahexaenoic Acid Coordinating with Sodium Selenite Promotes Paraptosis in Colorectal Cancer Cells by Disrupting the Redox Homeostasis and Activating the MAPK Pathway

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