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

Oksana Kutsyr, Agustina Noailles, Natalia Martínez‐Gil, Lucía Maestre‐Carballa, Manuel Martínez‐García, Victoria Maneu, Nicolás Cuenca, Pedro Lax

2021Proceedings of the National Academy of Sciences45 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

Retinitis pigmentosaRetinal degenerationOxidative stressRetinalRetinaPhotoreceptor cellBiologyInflammationInternal medicineProinflammatory cytokineEndocrinologyMedicineNeuroscienceBiochemistryRetinal Diseases and TreatmentsNeuroinflammation and Neurodegeneration MechanismsCytomegalovirus and herpesvirus research