[Retracted] Pinosylvin Extract Retinari™ Sustains Electrophysiological Function, Prevents Thinning of Retina, and Enhances Cellular Response to Oxidative Stress in NFE2L2 Knockout Mice

Abstract

Chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, which has been observed in age-related macular degeneration. We have previously shown an effective age-related macular degeneration disease model in mice with nuclear factor-erythroid 2-related factor-2 (NFE2L2) knockout. We have also shown pinosylvin, a polyphenol abundant in bark waste, to increase human retinal pigment epithelium cell viability in vitro. In this work, the effects of commercial natural pinosylvin extract, Retinari™, were studied on the electroretinogram, optical coherence tomogram, autophagic activity, antioxidant capacity, and inflammation markers. Wild-type and NFE2L2 knockout mice were raised until the age of 14.8 ± 3.8 months. They were fed with either regular or Retinari™ chow ( 141 ± 17.0 mg/kg/day of pinosylvin) for 10 weeks before the assays. Retinari™ treatment preserved significant retinal function with significantly preserved a- and b-wave amplitudes in the electroretinogram responses. Additionally, the treatment prevented thinning of the retina in the NFE2L2 knockout mice. The NFE2L2 knockout mice showed reduced ubiquitin-tagged protein accumulation in addition to local upregulation of complement factor H and antioxidant enzymes superoxide dismutase 1 and catalase. Therefore, the treatment in the NFE2L2 KO disease model led to reduced chronic oxidative stress and sustained retinal function and morphology. Our results demonstrate that pinosylvin supplementation could potentially lower the risk of age-related macular degeneration onset and slow down its progression.

Oxidative Stress and Cellular Protein Accumulation Are Present in Keratoconus, Macular Corneal Dystrophy, and Fuchs Endothelial Corneal Dystrophy

“…For example, NFE2L2 controls catalase and ALDH3, whereas FOXO (forkhead box transcription factor of the class O) and NF-κB (nuclear factor kappa B) regulate the expression of SOD enzymes [ 27 ]. Recently, pinosylvin, an analog of resveratrol, was found to activate both catalase and SOD1 in a mouse model of age-related macular degeneration possibly due to the dual effect of pinosylvin and its metabolite resveratrol on NFE2L2 and SOD regulating transcription factors, respectively [ 68 ]. Pinosylvin or a combination of molecules capable of activating the antioxidant defense system in a wide spectrum would possibly offer a higher impact on cellular wellbeing than molecules targeted to a single transcription factor.…”

Natural Sources and Pharmacological Properties of Pinosylvin

“…Considering that chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, as seen in AMD, Tamminen et al [85] investigated the effects of commercial natural pinosylvin extract, Retinari™, on electroretinogram, optical coherence tomogram, autophagic activity, antioxidant capacity, and inflammation markers in their study. For 10 weeks before the experiments, wild-type and NFE2L2 knockout mice were given either ordinary or Retinari™ chow.…”

Retracted: Pinosylvin Extract Retinari™ Sustains Electrophysiological Function, Prevents Thinning of Retina, and Enhances Cellular Response to Oxidative Stress in NFE2L2 Knockout Mice

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Manipulated or compromised peer review …”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”