Circadian Control and Pinosylvin Treatment in the Disease Model of Age‐related Macular Degeneration

• Published in: Acta ophthalmologica (Oxford, England) Vol. 97; no. S263
• Main Authors: Tamminen, Toni, Koskela, Ali, Toropainen, Elisa, Pitkänen, Marja, Viiri, Johanna, Paterno, Jussi, Seppänen, Anne, Koskelainen, Ari, Kaarniranta, Kai
• Format: Journal Article
• Language: English
• Published: Malden Wiley Subscription Services, Inc 01.12.2019
• Subjects: Age; Autophagy; Circadian rhythm; Circadian rhythms; Electroretinograms; Latency; Macular degeneration; Medical treatment; Oxidative stress; Pathogenesis; Phagocytosis; Pinosylvin; Protein interaction; Rodents; Visual perception
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2019.5255

Purpose Circadian clocks in the eye are critical for normal visual function and they relate to periodical renewal of photoreceptor outer segments as well as oxidative stress. Impaired rhythm can thus contribute to the pathogenesis of age‐related macular degeneration (AMD). Chronic oxidative stress leads eventually to protein aggregation in combination with impaired autophagy. We hypothesise that pinosylvin, a polyphenolic compound, slows down the progression of AMD through autophagy induction. Methods We investigated the relative change in electroretinogram (ERG) metrics of mice raised in 12:12 h light‐dark cycle and after a 24 h two‐week dark period in wild type (WT; n = 10), PGC1‐α knock‐out (KO; n = 7) and Nrf2 KO (n = 7) mice aged 9.7 ± 3.4 months. From these, 9 WT, 5 PGC1‐α and 7 Nrf2 KO mice continued to be raised to an age of 17.3 ± 3.8 months and assigned to a treatment and control group and fed for 2 months with pinosylvin‐feed or regular‐feed prior to recording ERG. Results The two‐week dark period resulted in significantly greater b‐wave amplitudes and shorter b‐wave latencies in WT mice in photopic ERG. Nrf2 KO and PGC1‐α/Nrf2 dKO mice exhibited b‐wave latency changes in the opposite. The dKO also had diminished b‐wave amplitudes. Scotopic ERG yielded no significant changes. Pinosylvin treatment in Nrf2 KO and PGC1‐α KO mice caused significantly increased b‐wave amplitudes in photopic ERG. In scotopic ERG, the pinosylvin treated mice had larger a‐ and b‐wave amplitudes in WT and Nrf2 KO mice, but not in PGC1‐α KO mice. Conclusions PGC1‐α KO and Nrf2 KO mice showed different circadian rhythmicity. Pinosylvin treatment showed improved ERG signalling in aged NRf2 KO and WT mice.