PUBLICATION

Gypenosides attenuate retinal degeneration in a zebrafish retinitis pigmentosa model

Authors
Alhasani, R.H., Zhou, X., Biswas, L., Li, X., Reilly, J., Zeng, Z., Shu, X.
ID
ZDB-PUB-201015-20
Date
2020
Source
Experimental Eye Research   201: 108291 (Journal)
Registered Authors
Keywords
Gypenosides, Photoreceptor death, RPGRIP1, Retinitis pigmentosa, Zebrafish
MeSH Terms
  • Animals
  • Gynostemma
  • Immunohistochemistry
  • Oxidative Stress*
  • Photoreceptor Cells, Invertebrate/drug effects*
  • Photoreceptor Cells, Invertebrate/metabolism
  • Photoreceptor Cells, Invertebrate/pathology
  • Plant Extracts/pharmacology
  • Reactive Oxygen Species/metabolism
  • Retina/drug effects*
  • Retina/metabolism
  • Retina/pathology
  • Retinitis Pigmentosa/drug therapy*
  • Retinitis Pigmentosa/metabolism
  • Retinitis Pigmentosa/pathology
  • Rhodopsin/metabolism
  • Zebrafish
(all 17)
PubMed
33049273 Full text @ Exp. Eye. Res.
Abstract
Retinitis pigmentosa (RP) is a collection of heterogenous genetic retinal disorders resulting in cumulative retinal deterioration involving progressive loss of photoreceptors and eventually in total blindness. Oxidative stress plays a central role in this photoreceptor loss. Gypenosides (Gyp) are the main functional component isolated from the climbing vine Gynostemma pentaphyllum and have been shown to defend cells against the effects of oxidative stress and inflammation, providing protection in experimentally-induced optic neuritis. The zebrafish model has been used to investigate a range of human diseases. Previously we reported early retinal degeneration in a mutant zebrafish line carrying a point-nonsense mutation in the retinitis pigmentosa GTPase regulator interacting protein 1 (rpgrip1) gene that is mutated in RP patients. The current study investigated the potential protective effects of Gyp against photoreceptor degeneration in the Rpgrip1 deleted zebrafish. Rpgrip1 mutant zebrafish were treated with 5 μg/ml of Gyp in E3 medium from 6 h post fertilization (hpf) till 1 month post fertilization (mpf). Rpgrip1 mutant zebrafish treated with 5 μg/mL of Gyp showed a significant decrease by 68.41% (p = 0.0002) in photoreceptor cell death compared to that of untreated mutant zebrafish. Expression of antioxidant genes catalase, sod1, sod2, gpx1, gclm, nqo-1 and nrf-2 was significantly decreased in rpgrip1 mutant zebrafish eyes by 61.51%, 77.40%, 60.11%, 81.17%, 72.07%, 78.95% and 85.42% (all p < 0.0001), respectively, when compared to that of wildtype zebrafish; superoxide dismutase and catalase activities, and glutathione levels in rpgrip1 mutant zebrafish eyes were significantly decreased by 87.21%, 21.55% and 96.51% (all p < 0.0001), respectively. There were marked increases in the production of reactive oxygen species (ROS) and malondialdehyde (MDA) by 2738.73% and 510.69% (all p < 0.0001), respectively, in rpgrip1 mutant zebrafish eyes; expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α was also significantly increased by 150.11%, 267.79% and 190.72% (all p < 0.0001), respectively, in rpgrip1 mutant zebrafish eyes, compared to that of wildtype zebrafish. Treatment with Gyp significantly counteracted these effects. This study indicates that Gyp has a potential role in the treatment of RP.
Genes / Markers
Marker Marker Type Name
atf4aGENEactivating transcription factor 4a
atf6GENEactivating transcription factor 6
blpGENEblowup
casp3aGENEcaspase 3, apoptosis-related cysteine peptidase a
catGENEcatalase
gclmGENEglutamate-cysteine ligase, modifier subunit
gpx1aGENEglutathione peroxidase 1a
hspa5GENEheat shock protein 5
il1bGENEinterleukin 1, beta
il6GENEinterleukin 6 (interferon, beta 2)
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Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fh314
    Point Mutation
    1 - 1 of 1
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    Human Disease / Model
    Human Disease Fish Conditions Evidence
    retinitis pigmentosarpgrip1fh314/fh314standard conditionsTAS
    1 - 1 of 1
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    Sequence Targeting Reagents
    Fish
    Antibodies
    Orthology
    Engineered Foreign Genes
    No data available
    Mapping