The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Abstract

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

Interactions between Apolipoprotein E Metabolism and Retinal Inflammation in Age-Related Macular Degeneration

“…Lifestyle or environmental factors, such as smoking (two-fold increased risk) and a high-fat diet, are associated with the development or progression of AMD and are thought to contribute to a pro-inflammatory environment via retinal oxidative stress [ 21 ]. Oxidative stress appears to drive the breakdown of the outer blood–retinal barrier, which is formed by tight junctions between RPE cells, leading to the infiltration of immune factors/cells and choroidal neovascularisation or atrophy [ 22 ]. Chronic oxidative stress in AMD may also cause impaired RPE autophagy, a physiological function that normally prevents the accumulation of oxidatively damaged organelles [ 23 ].…”

Retinal Dysfunction in Alzheimer’s Disease and Implications for Biomarkers

“…These findings imply that the blood-retina barrier mediates the retinal vascular disruption involved in AD and that retinal vascular parameters (e.g., vascular Aβ and PDGFRβ signaling) might be early signs of the occurrence of AD. Nevertheless, damage to the blood-retina barrier, which regulates retinal metabolism and vascular leakage, is a crucial factor in other retinal microvascular disorders such as AMD [120], diabetic macular edema [121], diabetic retinopathy [122], and uveitis [123]. Therefore, retinal vascular disruption may be nonspecific for AD detection.…”

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

“…The excessive production of free radicals, including reactive oxygen (ROS) and reactive nitrogen (RNS) species beyond the body’s antioxidant capacity to attenuate them results in a condition known as oxidative stress. This condition has been identified to play key roles in the initiation and progression of many disease conditions such as inflammatory bowel, cardiovascular, cerebrovascular and neurodegenerative diseases, many types of cancers [ 68 , 69 ], and age-related macular degeneration (AMD) [ 70 , 71 ]. To protect the human body from the wraths of free radicals generated from external and internal sources, the modification of dietary lifestyle to include the consumption of foods rich in radical-scavenging and antioxidant chemicals is highly encouraged [ 72 , 73 ].…”