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

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.

Spontaneous electroretinogram signals to screen people with early risk factors for diabetic retinopathy

“…These alterations were not accompanied by changes in OPs in high-fat diet-fed mice and in people with overweight, obesity, and MetS. These observations are consistent with previous studies in animal models 48,49 , but contrast with data showing reduced OP amplitude in high-fat diet-fed mice 50 or in ob/ob mice 51 . These discrepancies may be attributed to the different induction mechanisms of obesity, known to result in models with their own characteristics 52,53 .…”

Preventable risk factors for type 2 diabetes can be detected using noninvasive spontaneous electroretinogram signals

“…These alterations were not accompanied by changes in OPs in high-fat diet-fed mice and in people with overweight, obesity, and MetS. These observations are consistent with previous studies in animal models [ 66 , 67 ], but contrast with data showing reduced OP amplitude in high-fat diet-fed mice [ 68 ] or in ob/ob mice [ 69 ]. These discrepancies may be attributed to the different induction mechanisms of obesity, known to result in models with their own characteristics [ 38 , 70 ].…”

An Exploratory Study Provides Insights into MMP9 and Aβ Levels in the Vitreous and Blood across Different Ages and in a Subset of AMD Patients

“…As the odds of developing AMD are closely associated with modifiable risks such as the intake of unhealthy foods and alcohol as well as smoking [ 42 , 43 , 44 , 45 , 46 , 47 ], we used patient records to obtain lifestyle information in our cohorts including mean arterial pressure, smoking status and smoking pack years. Previous studies have examined the effects of blood pressure on the odds of developing AMD with inconsistent results [ 48 , 49 ], where hypertension plays an incompletely defined role in this multifactorial disease.…”

“…Our search also identified a family of molecules associated with lipid metabolism, which includes the very low-density lipoprotein receptor (VLDR), the low-density lipoprotein receptor (LDLR), and apolipoproteins A-I and -II, C-I and E as well as B. Dysregulated lipid metabolism is known to play an important role in retinal pathology [ 70 ] including mediating effects of poor nutrition, which is a modifiable AMD risk factor. For instance, we have previously shown how an unhealthy “Western-style” high-fat diet alone causes salient early-intermediate AMD-like features in wildtype mice including changes to retinal lipids [ 47 ], and how AMD-linked disease pathways associated with an unhealthy diet can cause specific RPE dysfunction [ 71 ]. Dysregulated lipid metabolism also plays an important role in Alzheimer’s pathology [ 72 ].…”