Abstract

Oxidative stress has a critical role in the pathogenesis of age-related macular degeneration (AMD), a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. The pathogenic mechanism of AMD is poorly understood. The ROS and nitrogen species produced during stress may damage crucial biomolecules of the retinal pigment epithelium (RPE) cells. There is a strong relation between stress oxidative and inflammatory response in the pathology of the AMD. Actually, there are many routes of oxidative stress related with AMD but the most representative are: autophagy/heterophagy, apoptosis, and iron, DNA and antioxidant enzymes. Autophagy is a cellular housekeeping process that removes damaged organelles and protein aggregates, whereas heterophagy, in the case of the RPE, is the phagocytosis of exogenous photoreceptor outer segments. Numerous studies have demonstrated that both autophagy and heterophagy are highly active in the RPE. Furthermore, the overexpression of CHOP can lead to cell cycle arrest and apoptosis, and activation of caspase cascades also occurs in ER stress. The αB crystallin is much studied because it has been shown to have antiapoptotic properties in RPE cells. Other possible cause is the excess iron in patients diagnosed AMD because induces tissue damage. These effects have been confirmed in rodent research with the downregulation of DNA repair enzymes involved in repair of oxidative damage occurred in aged RPE and choroid. Finally, the genetic defects (antioxidant enzymes), dietary or uptake deficiencies in antioxidants, or exposure to noxious agents (cigarette smoking) could enhance oxidative RPE damage during life and predispose to AMD. There are many routes related with oxidative stress and inflammatory response related with AMD patients. Antioxidant supplementation helped attenuate the development of choroidal new vessels but it is necessary to invest all mechanism of this ocular pathology to develop new therapies.

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