June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
High-fat consumption accelerates retinal degeneration and alters the gut microbiome in retinitis pigmentosa mice
Author Affiliations & Notes
  • Oksana Kutsyr
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Agustina Noailles
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Natalia Martínez-Gil
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Laura Fernández-Sánchez
    Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain
  • Lucía Maestre-Carballa
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Manuel Martínez-García
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Victoria Maneu
    Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain
  • Nicolas Cuenca
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Pedro Lax
    Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain
  • Footnotes
    Commercial Relationships   Oksana Kutsyr, None; Agustina Noailles, None; Natalia Martínez-Gil, None; Laura Fernández-Sánchez, None; Lucía Maestre-Carballa, None; Manuel Martínez-García, None; Victoria Maneu, None; Nicolas Cuenca, None; Pedro Lax, None
  • Footnotes
    Support  MINECOFEDER-BFU2015-67139-R, FEDER-PID2019-106230RB-I00, RETICS-FEDER RD16/0008/0016, IDIFEDER/2017/064.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3072. doi:
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      Oksana Kutsyr, Agustina Noailles, Natalia Martínez-Gil, Laura Fernández-Sánchez, Lucía Maestre-Carballa, Manuel Martínez-García, Victoria Maneu, Nicolas Cuenca, Pedro Lax; High-fat consumption accelerates retinal degeneration and alters the gut microbiome in retinitis pigmentosa mice. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3072.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The consumption of high-fat diets (HFD) can lead to significant changes in the gut microbiome. Likewise, intestinal dysbiosis has been associates with the pathogenesis of several degenerative diseases. Thus, the purpose of this work was to analyze the gut microbiome changes associated with the consumption of HFD in mice with retinitis pigmentosa (RP).

Methods : Healthy C57BL/6J mice and dystrophic rd10 mice (RP) were fed either with normal chow (5.5% fat kcal) or with a HFD (61.6% fat kcal) for two weeks after weaning (P19). At the endpoint, retinal function was evaluated by optomotor test and electroretinography. The structure and integrity of the retina were studied by immunohistochemistry. Additionally, the gut microbiome was analyzed by 16S rRNA gene sequencing.

Results : Increased retinal degeneration was found in rd10 mice compared to C57BL/6J mice, both fed with normal chow. rd10 mice showed significantly diminished retinal responsiveness, with lower a- and b-waves, as well as reduced visual acuity. The loss of retinal function was accompanied by a fall in the number of photoreceptor rows, and the remaining photoreceptors exhibited morphologic anomalies. Additionally, the photoreceptor degeneration was associated to an inflammatory response of the retina, with the proliferation of microglial cells and reactive gliosis of Müller cells. Moreover, the gut microbiome analysis revealed differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels. Notably, four common ASV (Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp.) in the gut of healthy animals were not found in the rd10 mice gut. HFD intake by rd10 mice resulted in a significant acceleration of the retinal function and morphology degeneration compared to rd10 mice fed normal chow. The consumption of HFD produced significant dysbiosis in the gut microbiome increasing potentially pro-inflammatory bacteria as Bilophila sp., Alistipes sp. and Mucispirillum schaedleri that probably contribute to the worsening of the degeneration process.

Conclusions : Retinal dysfunction and degeneration in retinitis pigmentosa is linked to significant changes in the gut microbiome, which can be further altered by diet, leading to a deterioration of the disease.

MINECOFEDER-BFU2015-67139-R, FEDER-PID2019-106230RB-I00, RETICS-FEDER RD16/0008/0016, IDIFEDER/2017/064.

This is a 2021 ARVO Annual Meeting abstract.

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