Evidence map›Paper›PMID 30114413›Full record

ArticleExperimental eye research2019

Lipid-derived and other oxidative modifications of retinal proteins in a rat model of Smith-Lemli-Opitz syndrome.

Rebecca J Kapphahn, Michael J Richards, Deborah A Ferrington, Steven J Fliesler

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental eye research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

4 authors at 3 institutions in 1 country.

Rebecca J KapphahnDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
Michael J RichardsDepartment of Ophthalmology, Saint Louis University, School of Medicine, St. Louis, MO, USA.
Deborah A FerringtonDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
Steven J FlieslerDepartment of Ophthalmology, Saint Louis University, School of Medicine, St. Louis, MO, USA; Departments of Ophthalmology and Biochemistry and the Neuroscience Graduate Program, The State University of New York (SUNY)- University at Buffalo, Buffalo, NY, USA; Research Service, Veterans Administration Western New York Healthcare System (VAWNYHS), Buffalo, NY, USA. Electronic address: fliesler@buffalo.edu.
University of Minnesota · USSaint Louis University · USVA Western New York Healthcare System · US

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
ISOPRENOID METABOLISM IN THE RETINAR01EY007361 · NEI · UNIVERSITY OF SOUTH FLORIDA · PI FLIESLER, STEVEN J. · 1988 to 2015
$4.4M
Proteasome Function in the Aging RetinaR01EY013623 · NEI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI FERRINGTON, DEBORAH ANN · 2003 to 2010
$2.2M
Immunoproteasome: A key component of the cellular stress responseR21AG032391 · NIA · UNIVERSITY OF MINNESOTA · PI FERRINGTON, DEBORAH ANN · 2008 to 2009
$315k
NCATS NIH HHS UL1 TR001412NEI NIH HHS R01 EY007361NEI NIH HHS R01 EY013623NIA NIH HHS R21 AG032391
6 · The paper itself

Abstract

Oxidative modification of proteins can perturb their structure and function, often compromising cellular viability. Such modifications include lipid-derived adducts (e.g., 4-hydroxynonenal (HNE) and carboxyethylpyrrole (CEP)) as well as nitrotyrosine (NTyr). We compared the retinal proteome and levels of such modifications in the AY9944-treated rat model of Smith-Lemli-Opitz syndrome (SLOS), in comparison to age-matched controls. Retinas harvested at 3 months of age were either subjected to proteomic analysis or to immuno-slot blot analysis, the latter probing blots with antibodies raised against HNE, CEP, and NTyr, followed by quantitative densitometry. HNE modification of retinal proteins was markedly (>9-fold) higher in AY9944-treated rats compared to controls, whereas CEP modification was only modestly (≤2-fold) greater, and NTyr modification was minimal and exhibited no difference as a function of AY9944 treatment. Anti-HNE immunoreactivity was greatest in the plexiform and ganglion cell layers, but also present in the RPE, choroid, and photoreceptor outer segment layer in AY9944-treated rats; control retinas showed minimal HNE labeling. 1D-PAGE/Western blot analysis of rod outer segment (ROS) membranes revealed HNE modification of both opsin and β-transducin. Proteomic analysis revealed the differential expression of several retinal proteins as a consequence of AY9944 treatment. Upregulated proteins included those involved in chaperone/protein folding, oxidative and cellular stress responses, transcriptional regulation, and energy production. βA3/A1 Crystallin, which has a role in regulation of lysosomal acidification, was down-regulated. Hence, oxidative modification of retinal proteins occurs in the SLOS rat model, in addition to the previously described oxidation of lipids. The results are discussed in the context of the histological and physiological changes that occur in the retina in the SLOS rat model.

Indexed as

Disease Models, AnimalOxidative StressAldehydesAnimalsBlotting, WesternElectrophoresis, Polyacrylamide GelEnzyme InhibitorsFemaleOpsinsPregnancyProteomicsRatsRats, Sprague-DawleyRetinaSmith-Lemli-Opitz Syndrometrans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride4-hydroxy-2-nonenalAldehydesEnzyme InhibitorsOpsinstrans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane DihydrochlorideTransducinCholesterolOxidationOxidative stressProtein modificationRetinaSmith-Lemli-Opitz

Identifiers

PMID30114413
PMCPMC6361703
OpenAlexW2886128934

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.