Evidence map›Paper›PMID 33811915›Full record

ArticleExperimental eye research2021

ON-bipolar cell gene expression during retinal degeneration: Implications for optogenetic visual restoration.

Michael J Gilhooley, Doron G Hickey, Moritz Lindner, Teele Palumaa, Steven Hughes, Stuart N Peirson, Robert E MacLaren, Mark W Hankins

Open access · hybridAbstract read
In one paragraph

Article in Experimental eye research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 29 citations in OpenAlex.

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  14. A systematic comparison of optogenetic approaches to visual restoration.Molecular therapy. Methods & clinical development · 2022
    Article
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  16. Article
  17. Article
  18. Review
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

8 authors at 3 institutions in 3 countries.

Michael J GilhooleyNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom; The Oxford Eye Hospital, Oxford, OX3 9DU, United Kingdom; Moorfields Eye Hospital, London, EC1V 2PD, United Kingdom.
Doron G HickeyNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom; Royal Victorian Eye and Ear Hospital, Melbourne, 002, Australia.
Moritz LindnerNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom; The Oxford Eye Hospital, Oxford, OX3 9DU, United Kingdom; Institute of Physiology and Pathophysiology, Department of Neurophysiology, Philipps University, Deutschhausstrasse 1-2, Marburg, 35037, Germany.
Teele PalumaaSleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom.
Steven HughesNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom; Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom.
Stuart N PeirsonSleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom.
Robert E MacLarenNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom; The Oxford Eye Hospital, Oxford, OX3 9DU, United Kingdom; Moorfields Eye Hospital, London, EC1V 2PD, United Kingdom.
Mark W HankinsNuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom; Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, OX1 3RE, United Kingdom. Electronic address: mark.hankins@eye.ox.ac.uk.
Nuffield Orthopaedic Centre · GBUniversity of Oxford · GBPhilipps University of Marburg · DE

Funding

Biotechnology and Biological Sciences Research Council BB/M009998/1Medical Research Council MR/S026266/1Wellcome Trust 205151/Z/16/Z
6 · The paper itself

Abstract

purposeRetinal bipolar cells survive even in the later stages of inherited retinal degenerations (IRDs) and so are attractive targets for optogenetic approaches to vision restoration. However, it is not known to what extent the remodelling that these cells undergo during degeneration affects their function. Specifically, it is unclear if they are free from metabolic stress, receptive to adeno-associated viral vectors, suitable for opsin-based optogenetic tools and able to propagate signals by releasing neurotransmitter.

methodsFluorescence activated cell sorting (FACS) was performed to isolate labelled bipolar cells from dissociated retinae of litter-mates with or without the IRD mutation Pde6b

resultsA total of sixty differentially expressed transcripts reached statistical significance: these did not include any genes directly associated with native primary bipolar cell signalling, nor changes consistent with metabolic stress. Four significantly altered genes (Srm2, Slf2, Anxa7 & Cntn1), implicated in synaptic remodelling, neurotransmitter release and viral vector entry had immunohistochemical staining colocalising with ON-bipolar cell markers and varying over the course of degeneration.

conclusionOur findings suggest relatively few gene expression changes in the context of degeneration: that despite remodelling, bipolar cells are likely to remain viable targets for optogenetic vision restoration. In addition, several genes where changes were seen could provide a basis for investigations to enhance the efficacy of optogenetic therapies.

Indexed as

AnimalsAnnexin A7Contactin 1DependovirusFemaleFlow CytometryGene Expression RegulationGenetic VectorsImmunohistochemistryMiceMice, TransgenicOptogeneticsReal-Time Polymerase Chain ReactionRetinal Bipolar CellsRetinal DegenerationSpermidine SynthaseAnnexin A7Anxa7 protein, mouseCntn1 protein, mouseContactin 1Spermidine SynthaseSulf2 protein, mouseSulfatasesBipolar cellGene expressionInherited retinal degenerationOptogenetics

Identifiers

PMID33811915
PMCPMC8214074
OpenAlexW3140993469

What OpenQuestion holds

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Registered trials

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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.