A High Fat “Western‐style” Diet Induces AMD‐Like Features in Wildtype Mice

Scope The intake of a “Western‐style” diet rich in fats is linked with developing retinopathies including age‐related macular degeneration (AMD). Wildtype mice are given a high fat diet (HFD) to determine how unhealthy foods can bring about retinal degeneration. Methods and results Following weaning...

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Published in:Molecular nutrition & food research 2022-06, Vol.66 (11), p.e2100823-n/a
Main Authors: Keeling, Eloise, Lynn, Savannah A., Koh, Yen Min, Scott, Jenny A., Kendall, Aaron, Gatherer, Maureen, Page, Anton, Cagampang, Felino R., Lotery, Andrew J., Ratnayaka, J. Arjuna
Format: Article
Language:English
Subjects:
age‐related macular degeneration (AMD)
blindness
Clusterin
Diet
Electroretinograms
Electroretinography
Endothelial cells
Epithelium
Etiology
Eye diseases
High fat diet
Histology
Immunofluorescence
Lipids
Macular degeneration
mouse models
Nutrition
Retina
Retinal degeneration
Retinal pigment epithelium
Tissue inhibitor of metalloproteinase 3
Transmission electron microscopy
unhealthy foods
Vacuoles
Weaning
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Summary:Scope The intake of a “Western‐style” diet rich in fats is linked with developing retinopathies including age‐related macular degeneration (AMD). Wildtype mice are given a high fat diet (HFD) to determine how unhealthy foods can bring about retinal degeneration. Methods and results Following weaning, female C57BL/6 mice are maintained on standard chow (7% kcal fat, n = 29) or a HFD (45% kcal fat, n = 27) for 12 months. Animals were sacrificed following electroretinography (ERG) and their eyes analyzed by histology, confocal immunofluorescence, and transmission electron microscopy. HFD mice become obese, but showed normal retinal function compared to chow‐fed controls. However, diminished β3tubulin labeling of retinal cross‐sections indicated fewer/damaged neuronal processes in the inner plexiform layer. AMD‐linked proteins clusterin and TIMP3 accumulated in the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Neutral lipids also deposited in the outer retinae of HFD mice. Ultrastructural analysis revealed disorganized photoreceptor outer segments, collapsed/misaligned RPE microvilli, vacuoles, convoluted basolateral RPE infolds and BrM changes. Basal laminar‐like deposits were also present alongside abnormal choroidal endothelial cells. Conclusions We show that prolonged exposure to an unhealthy “Western‐style” diet alone can recapitulate early‐intermediate AMD‐like features in wildtype mice, highlighting the importance of diet and nutrition in the etiology of sight‐loss. Wildtype C57BL/6 mice maintained for 12 months on a high fat “Western‐style” diet (45% kcal from fat) develop signs of retinal pathology, which are similar to patients in early‐intermediate stages of age‐related macular degeneration, the commonest form of blindness in developed societies. These findings show that an unhealthy diet alone can increase the odds of developing sight‐loss in later life.
ISSN:1613-4125
1613-4133
DOI:10.1002/mnfr.202100823