(3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one ameliorates retinal degeneration in Pde6brd10 mice

Cutan Ocul Toxicol. 2018 Sep;37(3):245-251. doi: 10.1080/15569527.2018.1441863. Epub 2018 Mar 15.

Abstract

As a severe photoreceptor-degenerative disease, retinitis pigmentosa (RP) is currently incurable and eventually leads to partial or complete blindness. (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) is a novel antioxidant isolated from the plant of Alpinia katsumadai Hayata, with protective effects on photoreceptor cells against lipoteichoic acid-induced damage through inhibiting oxidative stress. The present study was to further demonstrate whether TIM could ameliorate retinal degeneration of Pde6brd10 (rd10) mice, a mouse model of RP. rd10 mice were treated with TIM by intraperitoneal injection daily from postnatal Day 10 (P10) to P26. Retinal function was tested by electroretinography. Histology was evaluated by toluidine blue staining and TUNEL assay. Oxidative stress markers were measured by ELISA. Immunohistochemistry, real-time PCR, and western blotting were applied to explore the protective mechanism. Results showed TIM significantly improved the retinal function and decreased photoreceptor cell apoptosis in rd10 mice through reducing oxidative stress. For the first time, this study demonstrated the protective effects of TIM against retinal degeneration in rd10 mice, providing scientific rationale to use TIM treating the RP.

Keywords: (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one; oxidative stress; rd10 mice; retinal degeneration.

MeSH terms

  • Alpinia / chemistry*
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Cell Survival
  • Chromans / chemistry
  • Chromans / pharmacology*
  • Chromans / therapeutic use
  • Cyclic Nucleotide Phosphodiesterases, Type 6 / genetics
  • Disease Models, Animal
  • Electroretinography
  • Humans
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oxidative Stress / drug effects
  • Photoreceptor Cells, Vertebrate / drug effects*
  • Photoreceptor Cells, Vertebrate / pathology
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology

Substances

  • (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one
  • Antioxidants
  • Chromans
  • Plant Extracts
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • Pde6b protein, mouse