Effects of the topical administration of semaglutide on retinal neuroinflammation and vascular leakage in experimental diabetes
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 th...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:256708 |
| Acceso en línea: | https://ddd.uab.cat/record/256708 https://dx.doi.org/urn:doi:10.3390/biomedicines9080926 |
| Access Level: | acceso abierto |
| Palabra clave: | Diabetic retinopathy Semaglutide Retina Db/db mouse |
| Sumario: | 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. |
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