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Research
Jean-Baptiste CONART
Universite de Lorraine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6348-6165
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Background Rhegmatogenous retinal detachment (RD) involving the macula is a major cause of visual impairment despite high surgical success rate, mainly because of cone death. We and others have shown that cone loss occurs secondary to chronic inflammation in many retinal diseases, including age-related macular degeneration and retinitis pigmentosa. We here investigated the yet unknown mechanisms of inflammation-induced cone death in RD.
Methods Vitreous samples from patients with RD and from control patients with macular hole were analyzed to characterize the inflammatory response to RD. A mouse model of RD and retinal explants culture were then used to explore the mechanisms leading to cone death.
Results Analysis of vitreous samples shows that RD induces a marked inflammatory response with increased cytokine and chemokine expression in humans, which is closely mimicked by experimental murine RD. In this model, we demonstrate that myeloid cells and T-lymphocytes directly contribute to cone loss, as the inhibition of their accumulation by Thrombospondin 1 increased cone survival. We show that cones are highly dependent on glucose and insulin signaling for survival in vitro and that insulin, and the insulin sensitizers rosiglitazone and metformin, prevent RD-induced cone loss in vivo, despite the persistence of inflammation.
Conclusion Our results describe a new mechanism by which inflammation, likely through a combination of competition for glucose and the inhibition of insulin signaling, promotes cone death in RD. Therapeutic inhibition of inflammation and stimulation of insulin signaling might prevent RD-associated cone death until the RD can be surgically repaired and improve visual outcome after RD.
Trial registration: ClinicalTrials.gov Identifier NCT03318588
Keywords
retinal detachment, cone degeneration, inflammation, mononuclear phagocytes, insulin signaling
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View the published article at Journal of Neuroinflammation.
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Review #1 received
Received 17 Jun, 2020
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On 04 Jun, 2020
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On 03 Jun, 2020
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Subject Areas
Neurobiology of Disease
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A new preprint design is coming!
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See the published version of this preprint at Journal of Neuroinflammation.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Jean-Baptiste CONART
Universite de Lorraine
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6348-6165
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Neuroinflammation.
Version 1
Posted 29 May, 2020
No community comments so far
Editorial decision: Major Revision
On 24 Jul, 2020
Review #2 received
Received 23 Jul, 2020
Review #1 received
Received 17 Jun, 2020
Reviewer #2 agreed
On 04 Jun, 2020
Reviewer #1 agreed
On 03 Jun, 2020
Reviewers invited
Invitations sent on 02 Jun, 2020
Editor assigned
On 26 May, 2020
Submission checks complete
On 25 May, 2020
Editor invited
On 25 May, 2020
First submitted
On 22 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Neuroinflammation.
Background Rhegmatogenous retinal detachment (RD) involving the macula is a major cause of visual impairment despite high surgical success rate, mainly because of cone death. We and others have shown that cone loss occurs secondary to chronic inflammation in many retinal diseases, including age-related macular degeneration and retinitis pigmentosa. We here investigated the yet unknown mechanisms of inflammation-induced cone death in RD.
Methods Vitreous samples from patients with RD and from control patients with macular hole were analyzed to characterize the inflammatory response to RD. A mouse model of RD and retinal explants culture were then used to explore the mechanisms leading to cone death.
Results Analysis of vitreous samples shows that RD induces a marked inflammatory response with increased cytokine and chemokine expression in humans, which is closely mimicked by experimental murine RD. In this model, we demonstrate that myeloid cells and T-lymphocytes directly contribute to cone loss, as the inhibition of their accumulation by Thrombospondin 1 increased cone survival. We show that cones are highly dependent on glucose and insulin signaling for survival in vitro and that insulin, and the insulin sensitizers rosiglitazone and metformin, prevent RD-induced cone loss in vivo, despite the persistence of inflammation.
Conclusion Our results describe a new mechanism by which inflammation, likely through a combination of competition for glucose and the inhibition of insulin signaling, promotes cone death in RD. Therapeutic inhibition of inflammation and stimulation of insulin signaling might prevent RD-associated cone death until the RD can be surgically repaired and improve visual outcome after RD.
Trial registration: ClinicalTrials.gov Identifier NCT03318588
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Figure 2
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Figure 5
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