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Age-related macular degeneration: A two-level model hypothesis.
Prog Retin Eye Res. 2020 05; 76:100825.PR

Abstract

Age-related diseases, including age-related macular degeneration (AMD), are of growing importance in a world where population ageing has become a dominant global trend. Although a wide variety of risk factors for AMD have been identified, age itself remains by far the most important risk factor, making it an urgent priority to understand the connections between underlying ageing mechanisms and pathophysiology of AMD. Ageing is both multicausal and variable, so that differences between individuals in biological ageing processes are the focus of a growing number of pathophysiological studies seeking to explain how ageing contributes to chronic, age-related conditions. The aim of this review is to integrate the available knowledge on the pathophysiology of AMD within the framework of the biology of ageing. One highly significant feature of biological ageing is systemic inflammation, which arises as a second-level response to a first level of molecular damage involving oxidative stress, mutations etc. Combining these insights, the various co-existing pathophysiological explanations in AMD arrange themselves according to a two-level hypothesis. Accordingly, we describe how AMD can be considered the consequence of age-related random accumulation of molecular damage at the ocular level and the subsequent systemic inflammatory host response thereof. We summarize evidence and provide original data to enlighten where evidence is lacking. Finally, we discuss how this two-level hypothesis provides a foundation for thoughts and future studies in prevention, prognosis, and intervention.

Authors+Show Affiliations

The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.Clinical Eye Research Division, Department of Ophthalmology, Zealand University, Hospital, Roskilde and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.Clinical Eye Research Division, Department of Ophthalmology, Zealand University, Hospital, Roskilde and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.Clinical Eye Research Division, Department of Ophthalmology, Zealand University, Hospital, Roskilde and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: tlso@regionsjaelland.dk.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31899290

Citation

Rozing, Maarten P., et al. "Age-related Macular Degeneration: a Two-level Model Hypothesis." Progress in Retinal and Eye Research, vol. 76, 2020, p. 100825.
Rozing MP, Durhuus JA, Krogh Nielsen M, et al. Age-related macular degeneration: A two-level model hypothesis. Prog Retin Eye Res. 2020;76:100825.
Rozing, M. P., Durhuus, J. A., Krogh Nielsen, M., Subhi, Y., Kirkwood, T. B., Westendorp, R. G., & Sørensen, T. L. (2020). Age-related macular degeneration: A two-level model hypothesis. Progress in Retinal and Eye Research, 76, 100825. https://doi.org/10.1016/j.preteyeres.2019.100825
Rozing MP, et al. Age-related Macular Degeneration: a Two-level Model Hypothesis. Prog Retin Eye Res. 2020;76:100825. PubMed PMID: 31899290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-related macular degeneration: A two-level model hypothesis. AU - Rozing,Maarten P, AU - Durhuus,Jon A, AU - Krogh Nielsen,Marie, AU - Subhi,Yousif, AU - Kirkwood,Thomas Bl, AU - Westendorp,Rudi Gj, AU - Sørensen,Torben Lykke, Y1 - 2019/12/30/ PY - 2018/09/26/received PY - 2019/12/19/revised PY - 2019/12/26/accepted PY - 2020/1/4/pubmed PY - 2020/1/4/medline PY - 2020/1/4/entrez KW - Age-related macular degeneration KW - Ageing KW - Immune response KW - Inflammation KW - Two-level model SP - 100825 EP - 100825 JF - Progress in retinal and eye research JO - Prog Retin Eye Res VL - 76 N2 - Age-related diseases, including age-related macular degeneration (AMD), are of growing importance in a world where population ageing has become a dominant global trend. Although a wide variety of risk factors for AMD have been identified, age itself remains by far the most important risk factor, making it an urgent priority to understand the connections between underlying ageing mechanisms and pathophysiology of AMD. Ageing is both multicausal and variable, so that differences between individuals in biological ageing processes are the focus of a growing number of pathophysiological studies seeking to explain how ageing contributes to chronic, age-related conditions. The aim of this review is to integrate the available knowledge on the pathophysiology of AMD within the framework of the biology of ageing. One highly significant feature of biological ageing is systemic inflammation, which arises as a second-level response to a first level of molecular damage involving oxidative stress, mutations etc. Combining these insights, the various co-existing pathophysiological explanations in AMD arrange themselves according to a two-level hypothesis. Accordingly, we describe how AMD can be considered the consequence of age-related random accumulation of molecular damage at the ocular level and the subsequent systemic inflammatory host response thereof. We summarize evidence and provide original data to enlighten where evidence is lacking. Finally, we discuss how this two-level hypothesis provides a foundation for thoughts and future studies in prevention, prognosis, and intervention. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/31899290/Age-related_macular_degeneration:_A_two-level_model_hypothesis L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(19)30112-0 DB - PRIME DP - Unbound Medicine ER -
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