Novel Protective Effects of Cistanche Tubulosa Extract Against Low-Luminance Blue Light-Induced Degenerative Retinopathy

Cell Physiol Biochem. 2018;51(1):63-79. doi: 10.1159/000495162. Epub 2018 Nov 15.

Abstract

Background/aims: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo.

Methods: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation.

Results: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model.

Conclusion: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Keywords: Apoptosis; Blue light; Cistanche tubulosa extract; Retinal pigment epithelial cells.

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Caspase 3 / metabolism
  • Cistanche / chemistry
  • Cistanche / metabolism*
  • Hydrogen Peroxide / toxicity
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Light*
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Oxidative Stress / drug effects
  • Phosphorylation / drug effects
  • Phosphorylation / radiation effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Retina / drug effects
  • Retina / physiology
  • Retinal Degeneration / pathology
  • Retinal Degeneration / prevention & control
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / drug effects
  • Retinal Pigment Epithelium / metabolism

Substances

  • Plant Extracts
  • Protective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Hydrogen Peroxide
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Caspase 3