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Review

The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology

by
Juha M. T. Hyttinen
1,*,
Ram Kannan
2,
Szabolcs Felszeghy
3,4,
Minna Niittykoski
5,
Antero Salminen
6 and
Kai Kaarniranta
1,7
1
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
2
The Stephen J. Ryan Initiative for Macular Research (RIMR), Doheny Eye Institute, DVRC 203, 1355 San Pablo Street, Los Angeles, CA 90033, USA
3
Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
4
Institute of Dentistry, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
5
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
6
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
7
Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, 70029 KYS Kuopio, Finland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5800; https://doi.org/10.3390/ijms20225800
Submission received: 1 October 2019 / Revised: 14 November 2019 / Accepted: 14 November 2019 / Published: 18 November 2019
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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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.
Keywords: age-related macular degeneration; epithelial-to-mesenchymal transition; hypoxia; nuclear factor erythroid 2-related factor; oxidative stress; reactive oxygen species; retinal pigment epithelium age-related macular degeneration; epithelial-to-mesenchymal transition; hypoxia; nuclear factor erythroid 2-related factor; oxidative stress; reactive oxygen species; retinal pigment epithelium

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MDPI and ACS Style

Hyttinen, J.M.T.; Kannan, R.; Felszeghy, S.; Niittykoski, M.; Salminen, A.; Kaarniranta, K. The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology. Int. J. Mol. Sci. 2019, 20, 5800. https://doi.org/10.3390/ijms20225800

AMA Style

Hyttinen JMT, Kannan R, Felszeghy S, Niittykoski M, Salminen A, Kaarniranta K. The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology. International Journal of Molecular Sciences. 2019; 20(22):5800. https://doi.org/10.3390/ijms20225800

Chicago/Turabian Style

Hyttinen, Juha M. T., Ram Kannan, Szabolcs Felszeghy, Minna Niittykoski, Antero Salminen, and Kai Kaarniranta. 2019. "The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology" International Journal of Molecular Sciences 20, no. 22: 5800. https://doi.org/10.3390/ijms20225800

APA Style

Hyttinen, J. M. T., Kannan, R., Felszeghy, S., Niittykoski, M., Salminen, A., & Kaarniranta, K. (2019). The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology. International Journal of Molecular Sciences, 20(22), 5800. https://doi.org/10.3390/ijms20225800

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