Tags

Type your tag names separated by a space and hit enter

Secretory proteostasis of the retinal pigmented epithelium: Impairment links to age-related macular degeneration.
Prog Retin Eye Res. 2020 Apr 09 [Online ahead of print]PR

Abstract

Secretory proteostasis integrates protein synthesis, processing, folding and trafficking pathways that are essential for efficient cellular secretion. For the retinal pigment epithelium (RPE), secretory proteostasis is of vital importance for the maintenance of the structural and functional integrity of apical (photoreceptors) and basal (Bruch's membrane/choroidal blood supply) sides of the environment it resides in. This integrity is achieved through functions governed by RPE secreted proteins, which include extracellular matrix modelling/remodelling, angiogenesis and immune response modulation. Impaired RPE secretory proteostasis affects not only the extracellular environment, but leads to intracellular protein aggregation and ER-stress with subsequent cell death. Ample recent evidence implicates dysregulated proteostasis as a key factor in the development of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, and research aiming to characterise the roles of various proteins implicated in AMD-associated dysregulated proteostasis unveiled unexpected facets of the mechanisms involved in degenerative pathogenesis. This review analyses cellular processes unveiled by the study of the top 200 transcripts most abundantly expressed by the RPE/choroid in the light of the specialised secretory nature of the RPE. Functional roles of these proteins and the mechanisms of their impaired secretion, due to age and genetic-related causes, are analysed in relation to AMD development. Understanding the importance of RPE secretory proteostasis in relation to maintaining retinal health and how it becomes impaired in disease is of paramount importance for the development and assessment of future therapeutic advancements involving gene and cell therapies.

Authors+Show Affiliations

Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom. Electronic address: lparaoan@liverpool.ac.uk.Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom; Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.Eye Research Centre, Department of Ophthalmology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32278708

Citation

Paraoan, Luminita, et al. "Secretory Proteostasis of the Retinal Pigmented Epithelium: Impairment Links to Age-related Macular Degeneration." Progress in Retinal and Eye Research, 2020, p. 100859.
Paraoan L, Sharif U, Carlsson E, et al. Secretory proteostasis of the retinal pigmented epithelium: Impairment links to age-related macular degeneration. Prog Retin Eye Res. 2020.
Paraoan, L., Sharif, U., Carlsson, E., Supharattanasitthi, W., Mahmud, N. M., Kamalden, T. A., Hiscott, P., Jackson, M., & Grierson, I. (2020). Secretory proteostasis of the retinal pigmented epithelium: Impairment links to age-related macular degeneration. Progress in Retinal and Eye Research, 100859. https://doi.org/10.1016/j.preteyeres.2020.100859
Paraoan L, et al. Secretory Proteostasis of the Retinal Pigmented Epithelium: Impairment Links to Age-related Macular Degeneration. Prog Retin Eye Res. 2020 Apr 9;100859. PubMed PMID: 32278708.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Secretory proteostasis of the retinal pigmented epithelium: Impairment links to age-related macular degeneration. AU - Paraoan,Luminita, AU - Sharif,Umar, AU - Carlsson,Emil, AU - Supharattanasitthi,Wasu, AU - Mahmud,Nur Musfirah, AU - Kamalden,Tengku Ain, AU - Hiscott,Paul, AU - Jackson,Malcolm, AU - Grierson,Ian, Y1 - 2020/04/09/ PY - 2020/01/24/received PY - 2020/03/24/revised PY - 2020/03/26/accepted PY - 2020/4/13/pubmed PY - 2020/4/13/medline PY - 2020/4/13/entrez KW - Age-related macular degeneration AMD KW - Amyloid β KW - Angiogenesis KW - Apical KW - Basolateral KW - Cathepsins KW - Cystatin C KW - Cytokine KW - Degeneration KW - ECM KW - Leader sequence KW - Neurotrophic KW - Protease inhibitors KW - Proteases KW - Retinal pigment epithelium RPE KW - Secretion KW - Secretory proteostasis SP - 100859 EP - 100859 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Secretory proteostasis integrates protein synthesis, processing, folding and trafficking pathways that are essential for efficient cellular secretion. For the retinal pigment epithelium (RPE), secretory proteostasis is of vital importance for the maintenance of the structural and functional integrity of apical (photoreceptors) and basal (Bruch's membrane/choroidal blood supply) sides of the environment it resides in. This integrity is achieved through functions governed by RPE secreted proteins, which include extracellular matrix modelling/remodelling, angiogenesis and immune response modulation. Impaired RPE secretory proteostasis affects not only the extracellular environment, but leads to intracellular protein aggregation and ER-stress with subsequent cell death. Ample recent evidence implicates dysregulated proteostasis as a key factor in the development of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, and research aiming to characterise the roles of various proteins implicated in AMD-associated dysregulated proteostasis unveiled unexpected facets of the mechanisms involved in degenerative pathogenesis. This review analyses cellular processes unveiled by the study of the top 200 transcripts most abundantly expressed by the RPE/choroid in the light of the specialised secretory nature of the RPE. Functional roles of these proteins and the mechanisms of their impaired secretion, due to age and genetic-related causes, are analysed in relation to AMD development. Understanding the importance of RPE secretory proteostasis in relation to maintaining retinal health and how it becomes impaired in disease is of paramount importance for the development and assessment of future therapeutic advancements involving gene and cell therapies. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/32278708/Secretory_proteostasis_of_the_retinal_pigmented_epithelium:_Impairment_links_to_age-related_macular_degeneration L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(20)30031-8 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.