Diet Mimicking “Fast Food” Causes Structural Changes to the Retina Relevant to Age-Related Macular Degeneration

ABSTRACT

Introduction: Metabolic syndrome is a disorder characterized by a constellation of findings including truncal obesity, elevated blood pressure, abnormal cholesterol levels, and high blood glucose. Recent evidence suggests that metabolic syndrome may be associated with increased risk of age-related macular degeneration (AMD) and other eye diseases. Recently, C57BL/6J wild-type mice fed with a “fast food” diet consisting of high fat, cholesterol, and fructose-supplemented water showed unique systemic pathology consistent with metabolic syndrome and nonalcoholic steatohepatitis. Additionally, these mice showed higher levels of fibrosis, inflammation, endoplasmic reticulum stress, and mitochondrial dysfunction compared to mice fed with only a high-fat diet alone. Since similar pathways are activated in AMD, we sought to determine whether mice fed a “fast food” diet exhibited retinal changes.

Methods: 3-month-old wild-type mice were randomized to a standard chow (n = 11) or a “fast food” (n = 18) diet and fed for 9 months. At 1 year of age, tissues were collected and retinas were analyzed using transmission electron microscopy. Quantitative measures of Bruch’s membrane thickness and retinal pigment epithelium (RPE) cell counts were performed.

Results: “Fast food” fed mice showed ocular pathology relevant to various stages of AMD including basal laminar deposits, focal thickening of Bruch’s membrane, and a significant loss of RPE cells.

Discussion/conclusion: A wild-type mouse model of metabolic syndrome fed a “fast food” diet developed changes to the retina similar to some of the pathologic features seen in AMD. Further investigations into this and similar animal models as well as further epidemiological studies are needed to more clearly define the association between metabolic syndrome and AMD.

KEYWORDS:

• Drusen
• basal laminar deposits
• macular degeneration
• metabolic syndrome

Author contributions

Gavin W. Roddy – Concept and design, data review and analysis, writing of manuscript

Robert H. Rosa, Jr. – interpretation of data, editing of manuscript

Kimberly B. Viker – acquisition of data

Bradley H. Holman – acquisition of data

Cheryl R. Hann – acquisition of data

Anuradha Krishnan – acquisition of data, provision of study materials

Gregory J. Gores – acquisition of data, provision of study materials

Sophie J. Bakri – interpretation of data

Michael P. Fautsch – Concept and design, data review and analysis, editing of manuscript

Additional information

Funding

National Eye Institute grants [EY 21727 and EY26490]; Mayo Foundation, Rochester, MN; Liles Macular Degeneration Research Fund, Baylor Scott & White–Central Texas Foundation, Temple, TX; and Center for Scientific Review [21727, 26490].