A high fat "Western-style" diet induces AMD-like features in Wildtype mice
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, 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.
age-related macular degeneration (AMD), blindness, high fat diet, mouse models, unhealthy foods
e2100823
Keeling, Eloise
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Lynn, Savannah A
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Koh, Yen Min
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Scott, Jenny A
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Kendall, Aaron
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Gatherer, Maureen
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Page, Anton
76ebbfb8-4fe3-495c-afff-1f2f34977fee
Cagampang, Felino R
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Lotery, Andrew J
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Ratnayaka, J Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
1 June 2022
Keeling, Eloise
3207bbdb-d391-44af-8abc-a60c08dce45b
Lynn, Savannah A
177ed471-999b-4420-b6f6-d24a85b72524
Koh, Yen Min
74353440-15a1-49d6-a42b-023ad01e6844
Scott, Jenny A
a87a2601-b068-4a9a-993a-6bf7e3884d5a
Kendall, Aaron
f9c0f89a-600c-446e-acfd-adf119008a38
Gatherer, Maureen
b0aae216-21c4-4737-b042-865a65658f06
Page, Anton
76ebbfb8-4fe3-495c-afff-1f2f34977fee
Cagampang, Felino R
7cf57d52-4a65-4554-8306-ed65226bc50e
Lotery, Andrew J
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Ratnayaka, J Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Keeling, Eloise, Lynn, Savannah A, Koh, Yen Min, Scott, Jenny A, Kendall, Aaron, Gatherer, Maureen, Page, Anton, Cagampang, Felino R, Lotery, Andrew J and Ratnayaka, J Arjuna
(2022)
A high fat "Western-style" diet induces AMD-like features in Wildtype mice.
Molecular Nutrition & Food Research, 66 (11), , [2100823].
(doi:10.1002/mnfr.202100823).
Abstract
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.
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Accepted/In Press date: 19 March 2022
e-pub ahead of print date: 19 March 2022
Published date: 1 June 2022
Additional Information:
Funding Information:
The authors thank Dr Matthew MacGregor Sharp (University of Southampton) for providing perfusion fixed mouse tissues from the laboratory of Dr Felino R. Cagampang (FRC). They also thank Jon Ward (Histochemistry Research Unit, University of Southampton) for his expertise in H&E and lipid stains. They are grateful to Professor Robert F. Mullins (University of Iowa, USA) for his help with interpreting TEM data. This work was funded by awards to JAR from the UK Macular Society, the NC3R (National Centre for the Replacement Refinement & Reduction of animals in research, NC/L001152/1) and the Gift of Sight Appeal.
Funding Information:
The authors thank Dr Matthew MacGregor Sharp (University of Southampton) for providing perfusion fixed mouse tissues from the laboratory of Dr Felino R. Cagampang (FRC). They also thank Jon Ward (Histochemistry Research Unit, University of Southampton) for his expertise in H&E and lipid stains. They are grateful to Professor Robert F. Mullins (University of Iowa, USA) for his help with interpreting TEM data. This work was funded by awards to JAR from the UK Macular Society, the NC3R (National Centre for the Replacement Refinement & Reduction of animals in research, NC/L001152/1) and the Gift of Sight Appeal.
Publisher Copyright:
© 2022 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.
Keywords:
age-related macular degeneration (AMD), blindness, high fat diet, mouse models, unhealthy foods
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Local EPrints ID: 457039
URI: http://eprints.soton.ac.uk/id/eprint/457039
ISSN: 1613-4133
PURE UUID: db1db950-3e7e-4e6a-a00f-966c0d04fbad
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Date deposited: 19 May 2022 17:00
Last modified: 17 Mar 2024 03:56
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Contributors
Author:
Eloise Keeling
Author:
Savannah A Lynn
Author:
Yen Min Koh
Author:
Jenny A Scott
Author:
Aaron Kendall
Author:
Maureen Gatherer
Author:
Anton Page
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