Influence of Chronic Intermittent Hypoxia on Neuroinflammation in AMD
Principal Investigator
Project Goals
It has recently been shown that patients with sleep apnea syndrome (SAS) suffer more frequently from age-related macular degeneration (AMD), but the reason for the association of both diseases remains obscure. Our preliminary data suggest that the episodes of hypoxia that characterize sleep apnea activate circulating immune cells and lead to longer and stronger detrimental inflammation in the eye in AMD models. Our project to study immune cell activation and detrimental inflammation by hypoxia might help explain the association of sleep apnea with AMD, and also that of other diseases, such as Alzheimer disease, that are associated with SAS and harmful inflammation. Increased awareness of this mechanism will help to diagnose and treat SAS in affected AMD patients, reducing their need for intravitreal injections and slowing the macular degeneration in the future.
Project Summary
AMD is a multifactorial disease that is due to the unfortunate interaction of genetic risk factors and environmental factors. We have previously shown how a variant of the complement factor H (CFH), which is the strongest inherited risk factor, impedes with the physiological clearance of retinal macrophages and encourages chronic, detrimental inflammation. Sleep apnea syndrome, characterized by episodes of chronic intermittent hypoxia, is very common in the elderly, and has recently been demonstrated to be an important environmental risk factor for debilitating late AMD. The reason for this association is unknown. Our preliminary data suggest that hypoxia that characterize sleep apnea, activates circulating immune cells and lead to increased expression of inflammatory cytokines and CFH that promote longer and stronger detrimental inflammation in the eye in AMD. We will study how experimental sleep apnea induces systemic immune cell activation and detrimental inflammation in the eye. Ultimately this work will improve our understanding of how the interplay of AMD risk factors induce debilitating late AMD, the basis for the development of new efficient therapies.
First published on: August 10, 2018
Last modified on: December 22, 2024