Pinosylvin extract Retinari™ sustains electrophysiological function, prevents thinning of retina and enhances cellular response to oxidative stress in NFE2L2 knock‐out mice

• Published in: Acta ophthalmologica (Oxford, England) Vol. 100; no. S267
• Main Authors: Tamminen, Toni, Koskela, Ali, Toropainen, Elisa, Gurubaran, Iswariyaraja Sridevi, Winiarczyk, Mateusz, Liukkonen, Mikko, Paterno, Jussi J., Lackman, Petri, Sadeghi, Amir, Viiri, Johanna, Hyttinen, Juha M. T., Koskelainen, Ari, Kaarniranta, Kai
• Format: Journal Article
• Language: English
• Published: Malden Wiley Subscription Services, Inc 01.01.2022
• Subjects: Antioxidants; Autophagy; Catalase; Cell viability; Clinical trials; Complement factor H; Electroretinograms; Inflammation; Macular degeneration; Oxidative stress; Pinosylvin; Protein interaction; Retina; Retinal pigment epithelium; Superoxide dismutase; Thinning; Ubiquitin
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2022.008

Purpose Chronic oxidative stress eventually leads to protein aggregation in combination with impaired autophagy, which has been observed in age‐related macular degeneration (AMD). We have recently developed a dry AMD mice model with a nuclear factor‐erythroid 2‐related factor‐2 (NFE2L2) knock‐out (KO). Pinosylvin, a polyphenol abundant in bark waste, improves retinal pigment epithelial cell (RPE) cell viability in vitro. Therefore, one can estimate that pinosylvin slow down the progression of dry AMD. Methods We investigated the effects of commercial natural pinosylvin extract, Retinari™, on the electroretinogram, optical coherence tomogram, autophagic activity, antioxidant capacity, and inflammation markers. Wild type (WT) and NFE2L2 KO mice were raised in 12:12 until the age of 14.8 ± 3.8 months. They were fed with either regular or Retinari™ chow (50–250 mg/kg/day of pinosylvin) for 10 weeks before the assays. Results Retinari™ treatment preserved significant retinal function in scotopic and photopic ERG and prevented thinning of the retina in the NFE2L2 KO mice. The NFE2L2 KO mice showed reduced ubiquitin‐tagged protein accumulation in addition to upregulation of the antioxidant enzymes superoxide dismutase 1 and catalase. Furthermore, the treatment seemed to reduce inflammation in NFE2L2 KO mice by causing a climb in the concentration of complement factor H. Conclusions Our results demonstrate a strong protective effect of Retinari™ on the AMD disease model. We believe that pinosylvin in the Retinari™ elicits the positive effects. Thus, pinosylvin could potentially lower the risk of AMD onset and slow down its progression for which clinical trials with the compound are highly anticipated.