Insulin inhibits inflammation-induced cone death in retinal detachment
| Autor: | Conart, Jean-Baptiste, Blot, Guillaume, Augustin, Sébastien, Millet-Puel, Géraldine, Roubeix, Christophe, Beguier, Fanny, Charles-Messance, Hugo, Touhami, Sara, Sahel, José-Alain, Berrod, Jean-Paul, Léveillard, Thierry, Guillonneau, Xavier, Delarasse, Cécile, Sennlaub, Florian |
|---|---|
| Přispěvatelé: | Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male genetic structures [SDV]Life Sciences [q-bio] Cone degeneration lcsh:RC346-429 Rosiglitazone Mice Thioredoxins Animals Humans Hypoglycemic Agents Insulin Eye Proteins lcsh:Neurology. Diseases of the nervous system Inflammation Cell Death Research Mononuclear phagocytes Middle Aged Metformin [SDV] Life Sciences [q-bio] Mice Inbred C57BL Insulin signaling Glucose Retinal detachment Retinal Cone Photoreceptor Cells Female sense organs |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, BioMed Central, 2020, 17 (1), ⟨10.1186/s12974-020-02039-1⟩ Journal of Neuroinflammation, Vol 17, Iss 1, Pp 1-15 (2020) Journal of Neuroinflammation, 2020, 17 (1), ⟨10.1186/s12974-020-02039-1⟩ |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/s12974-020-02039-1⟩ |
| Popis: | 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. RD causes the infiltration of activated immune cells, but it is not clear whether and how infiltrating inflammatory cells contribute to cone cell loss. 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 confirms 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 corroborate that myeloid cells and T-lymphocytes contribute to cone loss, as the inhibition of their accumulation by Thrombospondin 1 (TSP1) increased cone survival. Using monocyte/retinal co-cultures and TSP1 treatment in RD, we demonstrate that immune cell infiltration downregulates rod-derived cone viability factor (RdCVF), which physiologically regulates glucose uptake in cones. Insulin and the insulin sensitizers rosiglitazone and metformin prevent in part the RD-induced cone loss in vivo, despite the persistence of inflammation Conclusion Our results describe a new mechanism by which inflammation induces cone death in RD, likely through cone starvation due to the downregulation of RdCVF that could be reversed by insulin. Therapeutic inhibition of inflammation and stimulation of glucose availability in cones by 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 NCT03318588 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink