2020/12/10
Keio University School of Medicine
A research group centered around Professor Kazuo Tsubota, Project Associate Professor Yoko Ozawa (concurrently a Research Professor at St. Luke's International University), and Lecturer Norihiro Nagai of the Department of Ophthalmology, and Professor Hideyuki Okano of the Department of Physiology, all from the Keio University School of Medicine, has successfully prevented the progression of the disease and restored visual function in model mice with age-related macular degeneration. The mice, which were developed by being fed a continuous high-fat diet, were administered an Angiotensin II type 1 receptor blocker (ARB), a medication also used to treat hypertension.
Age-related macular degeneration is the fourth leading cause of blindness in Japan. As it develops from the long-term accumulation of inflammation and oxidative stress, prevention is crucial, which involves avoiding risk factors such as excessive intake of high-fat foods and smoking. This study demonstrated that a continuous high-fat diet causes lipids (oxidized low-density lipoprotein [oxidized LDL], including cholesterol) to accumulate in inflammatory cells called macrophages. These activated macrophages then gather in localized areas of the retina, causing inflammation that degenerates the retinal pigment epithelium and leads to a decline in visual function. Furthermore, the study showed that all of these conditions could be reversed with daily administration of ARBs. It also revealed that lipid accumulation in macrophages from a high-fat diet is due to a decrease in the expression of ABCA1, a transporter essential for cholesterol efflux. This decrease is caused by the suppression of a series of molecular expressions under lipid-loading stimulation. The study showed that ARBs work to maintain ABCA1 expression by restoring this upstream signaling.
The results of this study suggest that ARBs may be effective in preventing the progression of age-related macular degeneration. It is hoped that these findings will lead to the development of new preventive treatments for age-related macular degeneration in modern populations who often consume high-fat diets.
The results of this research were published in the online edition of "Communications Biology" on December 9, 2020 (UK time).
Please see below for the full press release.