[Frontiers in Bioscience 17, 1976-1995, January 1, 2012]

Oxidative stress: The achilles' heel of neurodegenerative diseases of the retina

Xue Cai1, James F. McGinnis1,2,3

1Department of Ophthalmology, Dean McGee Eye Institute, 2Department of Cell Biology, 3Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104


1. Abstract
2. Introduction
3. Characteristics of macular degeneration
4. Mechanisms of AMD
4.1. Hereditary effect (genetic variations)
4.1.1.Complement system
4.1.2. Other genes and DNA variations
4.2. Oxidative stress, inflammation and ER stress
4.3. Cigarette smoking
4.4. Other factors for AMD
5. Animal models of AMD
5.1. Dry AMD models
5.2. Wet AMD models
5.3. Both dry and wet AMD models
6. Therapies for AMD
6.1. Pharmacological treatment
6.1.1. Antioxidant treatment
6.1.2. Antiangiogenic treatment
6.2. Gene therapy
6.3. Regenerative medicine
6.4. Nanomedicine
7. Conclusions and perspectives
8. Acknowledgements
9. References


Age-related macular degeneration (AMD) is the leading cause of blindness among adults in the developed countries. It is characterized by the progressive loss of central vision. AMD is classified into two forms: dry and wet. Dry AMD involves the accumulation of deposits in the RPE and Bruch's membrane; Wet AMD is characterized by neovascularization in the choroid. Whether the two forms of AMD share the same mechanism for the disease development is presently not clear. Oxidative stress, inflammation, and ER-stress are the common modes for the pathogenesis of AMD. In addition, other risk factors and several signaling pathways have been implicated as causative factors of AMD. In this paper, the mechanisms underlying AMD, risk factors involved in the pathology, representative animal models, and therapeutic treatment strategies are reviewed.