Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
Simó Canonge, Rafael (Hospital Universitari Vall d'Hebron)
Bogdanov, Patricia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ramos, Hugo (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Huerta, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Simó-Servat, Olga (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernández, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	Background: An unexpected increase in the rate of severe diabetic retinopathy was observed in the Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN)-6 clinical trial. Although this effect was attributed to a rapid decrease in blood glucose levels, a direct deleterious effect of semaglutide on the retina could not be ruled out. In order to shed light on this issue, we have performed a study aimed at testing the direct effect of semaglutide administered by eye drops on retinal neuroinflammation and microvascular abnormalities using the db/db mouse model. Methods: Eye drops containing semaglutide (0. 33 mg/mL; 5 µL once/daily) or vehicle (PBS; 5 µL once daily) were administered for 15 days. Results: We found that semaglutide significantly reduced glial activation, as well as the retinal expression of Nuclear factor kB (NF-κB), proinflammatory cytokines (IL-1β, IL-6, IL-18) and Intercellular Adhesion Molecule (ICAM)-1. In addition, semaglutide prevented the apoptosis of cells from the retinal ganglion layer and activated the protein kinase B (AKT) pathway. Finally, a dramatic decrease in vascular leakage was observed in db/db mice treated with semaglu-tide. All these findings were observed without any change in blood glucose levels and, therefore, can be directly attributed to semaglutide. Conclusions: These experimental findings point to a beneficial rather than a deleterious effect of semaglutide on the retina of subjects with diabetes. 0926.
Ayudas:	Ministerio de Economía y Competitividad 201629-10 Ministerio de Economía y Competitividad PI16/00541 Instituto de Salud Carlos III PI19/01215 Ministerio de Economía y Competitividad SAF2016-77784
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Diabetic retinopathy ; Semaglutide ; Retina ; Db/db mouse
Publicado en:	Biomedicines, Vol. 9 Núm. 8 (august 2021) , p. 926, ISSN 2227-9059

DOI: 10.3390/biomedicines9080926
PMID: 34440130

10 p, 2.4 MB

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