Premium
A High Fat “Western‐style” Diet Induces AMD‐Like Features in Wildtype Mice
Author(s) -
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
Publication year - 2022
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.202100823
Subject(s) - retinal , electroretinography , retinal pigment epithelium , macular degeneration , biology , retina , retinal degeneration , medicine , endocrinology , ophthalmology , biochemistry , neuroscience
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.