Evidence map›Paper›PMID 26344735›Full record

ReviewProgress in retinal and eye research2016

Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration.

Deborah A Ferrington, Debasish Sinha, Kai Kaarniranta

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Progress in retinal and eye research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 3 pooled it
15.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 3 syntheses or guidelines pooled it, 234 citations in OpenAlex.

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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 3 institutions in 2 countries.

Deborah A FerringtonDepartment of Ophthalmology and Visual Neurosciences, 2001 6th St SE, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: ferri013@umn.edu.
Debasish SinhaWilmer Eye Institute, The Johns Hopkins University School of Medicine, Room M035 Robert and Clarice Smith Bldg, 400 N Broadway, Baltimore, MD, 21287, USA. Electronic address: debasish@jhmi.edu.
Kai KaarnirantaDepartment of Ophthalmology, University of Eastern Finland and Kuopio University Hospital, P.O. Box 100, 70029 KYS, Finland. Electronic address: kai.kaarniranta@uef.fi.
Johns Hopkins Medicine · USUniversity of Eastern Finland · FIUniversity of Minnesota · US

Funding

A novel bA3/A1-crystallin gene mutation results in persistent fetal vasculatureR01EY019037 · NEI · JOHNS HOPKINS UNIVERSITY · PI SINHA, DEBASISH · 2008 to 2015
$4.1M
NEI NIH HHS EY019037NEI NIH HHS EY019037-SNEI NIH HHS R01 EY019037
6 · The paper itself

Abstract

Maintenance of protein homeostasis, also referred to as "Proteostasis", integrates multiple pathways that regulate protein synthesis, folding, translocation, and degradation. Failure in proteostasis may be one of the underlying mechanisms responsible for the cascade of events leading to age-related macular degeneration (AMD). This review covers the major degradative pathways (ubiquitin-proteasome and lysosomal involvement in phagocytosis and autophagy) in the retinal pigment epithelium (RPE) and summarizes evidence of their involvement in AMD. Degradation of damaged and misfolded proteins via the proteasome occurs in coordination with heat shock proteins. Evidence of increased content of proteasome and heat shock proteins in retinas from human donors with AMD is consistent with increased oxidative stress and extensive protein damage with AMD. Phagocytosis and autophagy share key molecules in phagosome maturation as well as degradation of their cargo following fusion with lysosomes. Phagocytosis and degradation of photoreceptor outer segments ensures functional integrity of the neural retina. Autophagy rids the cell of toxic protein aggregates and defective mitochondria. Evidence suggesting a decline in autophagic flux includes the accumulation of autophagic substrates and damaged mitochondria in RPE from AMD donors. An age-related decrease in lysosomal enzymatic activity inhibits autophagic clearance of outer segments, mitochondria, and protein aggregates, thereby accelerating the accumulation of lipofuscin. This cumulative damage over a person's lifetime tips the balance in RPE from a state of para-inflammation, which strives to restore cell homeostasis, to the chronic inflammation associated with AMD.

Indexed as

ProteolysisAnimalsAutophagyHumansLysosomesMacular DegenerationPhagocytosisProteasome Endopeptidase ComplexRetinal Pigment EpitheliumUbiquitin-Protein Ligase ComplexesProteasome Endopeptidase ComplexUbiquitin-Protein Ligase ComplexesAge-related macular degenerationAutophagyLysosomeProteasomeProteostasisRetinal pigment epithelium

Identifiers

PMID26344735
PMCPMC4769684
OpenAlexW1438640379

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.