Short-term high-fat feeding exacerbates degeneration in retinitis pigmentosa by promoting retinal oxidative stress and inflammation

A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystroph...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2021-10, Vol.118 (43), p.1-12
Main Authors: Kutsyr, Oksana, Noailles, Agustina, Martínez-Gil, Natalia, Maestre-Carballa, Lucía, Martinez-Garcia, Manuel, Maneu, Victoria, Cuenca, Nicolás, Lax, Pedro
Format: Article
Language:English
Subjects:
Acuity
Acute effects
Animals
Biological Sciences
Cell activation
Cell Death
Consumption
Degeneration
Diet, High-Fat - adverse effects
Disease Models, Animal
Dysbacteriosis
Electroretinography
Feeding
Female
Gastrointestinal Microbiome
Gliosis
Glucose Intolerance
High fat diet
Hyperglycemia
Inflammation
Intestinal microflora
Male
Metabolic disorders
Metabolic syndrome
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Microbiomes
Models, Biological
Morphology
Oxidative Stress
Photoreceptor Cells, Vertebrate - pathology
Retina
Retina - metabolism
Retina - pathology
Retinal degeneration
Retinal Degeneration - etiology
Retinal Degeneration - metabolism
Retinal Degeneration - pathology
Retinitis
Retinitis pigmentosa
Retinitis Pigmentosa - etiology
Retinitis Pigmentosa - metabolism
Retinitis Pigmentosa - pathology
Visual acuity
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Summary:A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystrophic retinal degeneration 10 (rd10) mice, a model of retinitis pigmentosa, fed an HFD for 2 to 3 wk. Short-term HFD feeding impaired retinal responsiveness and visual acuity and enhanced photoreceptor degeneration, microglial cell activation, and Müller cell gliosis. HFD consumption also triggered the expression of inflammatory and oxidative markers in rd10 retinas. Finally, an HFD caused gut microbiome dysbiosis, increasing the abundance of potentially proinflammatory bacteria. Thus, HFD feeding drives the pathological processes of retinal degeneration by promoting oxidative stress and activating inflammatory-related pathways. Our findings suggest that consumption of an HFD could accelerate the progression of the disease in patients with retinal degenerative disorders.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2100566118