Abstract
Age-related macular degeneration (AMD) is a mounting cause of loss of sight in the elderly in the developed countries, a trend enhanced by the continual ageing of the population. AMD is a multifactorial and only partly understood, malady. Unfortunately, there is no effective treatment for most AMD patients. It is known that oxidative stress (OS) damages the retinal pigment epithelium (RPE) and contributes to the progression of AMD. We review here the potential importance of two OS-related cellular systems in relation to AMD. First, the nuclear factor erythroid 2-related factor 2 (NFE2L2; NRF2)-mediated OS response signalling pathway is important in the prevention of oxidative damage and a failure of this system could be critical in the development of AMD. Second, epithelial-to-mesenchymal transition (EMT) represents a change in the cellular phenotype, which ultimately leads to the fibrosis encountered in RPE, a characteristic of AMD. Many of the pathways triggering EMT are promoted by OS. The possible interconnections between these two signalling routes are discussed here. From a broader perspective, the control of NFE2L2 and EMT as ways of preventing OS-derived cellular damage could be potentially valuable in the therapy of AMD.
Highlights
oxidative stress (OS) is responsible for much of the damage connected to the initiation and progression of Age-related macular degeneration (AMD) and if there were a means of controlling this excessive OS, it could provide a novel approach to treat this disease
The epithelial-to-mesenchymal transition (EMT) transition, our other topic, is a feature of foetal development and cancer expansion but in fibrosis, it is usually associated with excessive wound healing processes and these have been linked to the damage to the retinal pigment epithelium (RPE) layer that occurs during AMD progression, especially of its wet form
The control of oxidation-induced EMT, via the various pathways related to OS, could be one way to avoid or diminish the damage to the RPE, perhaps in the therapy of the wet type AMD but possibly in combatting the much more common dry AMD
Summary
Age-related macular degeneration (AMD) is the principal cause of visual loss in the developed countries and, since its incidence increases steadily with age, the affected population shows a continual increase [1]. In the eyes of these animals, many signs of disturbed clearance, accumulated deposits, RPE degeneration and, age-related visual loss are seen These findings link the damage to NFE2L2 gene deficiency in the pathogenesis of AMD [40,41]. The second pathway, which is linked to OS, is the epithelial-to-mesenchymal transition (EMT) (Section 3), a shift in the cellular phenotype, that is, the cell changes from being polarised, layered and immobile to a non-layered, spindle-like cell which is capable of migration Both of these systems are thought to be connected with cellular changes and damage in the retina and have been linked with age-related diseases, such as AMD. The Kelch-Like ECH-Associated Protein 1 (KEAP1)-Nuclear Factor Erythroid 2-Rlated Factor (NFE2L2) Pathway
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