Age-related macular degeneration (AMD) is a prevalent eye disease that is responsible for more than 5% of all the legal blindness cases. AMD is classified into two primary forms: wet and dry AMD. While treatments exist for the wet variant of AMD, which significantly improve symptoms, there is currently no treatment for the dry form, which affects the majority of patients. Factors such as dyslipidemia, hyperglycemia and diabetes are believed to contribute to AMD's development. Diet-induced animal models provide an effective platform for studying the influence of these factors on AMD. Rabbits are the most common model for testing ocular drug safety and are susceptible to high-fat diets. A study in Disease Models & Mechanisms explores how different diets affect the retinal phenotypes of Chinchilla rabbits.

Neither a high-sugar diet (HSD) nor a high-fat diet (HFD) alone affected electroretinograms when compared to control animals. However, when these diets were combined into a high-fat high-sugar diet (HFSD), significant disruptions were observed across all electroretinogram waves, indicating inhibited retinal function. In addition to functional impairment, the combination diet caused notable retinal lesions and pigment abnormalities compared to controls. It also led to an accumulation of lipid droplets around the retina and activated microglia, processes that contributed to retinal degeneration. RNA sequencing of retinal cells from animals across all dietary groups revealed that all three experimental diets influenced the Apelin pathway. This pathway is closely linked to energy metabolism, suggesting that these diets induce considerable metabolic changes in the retinal cells of rabbits, promoting the progression of retinal dysfunction.

These results show that diet can influence the progression of dry AMD, especially high-fat, high-sugar diets, which are prevalent in today’s world. Additionally, male chinchilla rabbits seem to be an appropriate model for dry AMD. Leveraging this knowledge, future studies can study the mechanisms behind the development of the disease more in depth while using dietary changes as a potential prevention against dry AMD.

Original reference: Wang, Y. et al. Dis. Model. Mech. 17, dmm052015 (2024)