Characterization of NLRP3 Inflammasome Activation in the Onset of Diabetic Retinopathy

• Published in: International journal of molecular sciences 2022-11, Vol.23 (22), p.14471
• Main Authors: Kuo, Charisse Y-J, Maran, Jack J, Jamieson, Emma G, Rupenthal, Ilva D, Murphy, Rinki, Mugisho, Odunayo O
• Format: Article
• Language: English
• Subjects: activation; Binding; Caspase 1 - metabolism; Caspase-1; Cell size; Connexin 43; Cytokines; Cytotoxicity; Diabetes; Diabetes Mellitus; Diabetic retinopathy; Diabetic Retinopathy - etiology; Diabetic Retinopathy - metabolism; Glial fibrillary acidic protein; human; Humans; Hyperglycemia; Immunohistochemistry; inflammasome; Inflammasomes; Inflammasomes - metabolism; Interleukin 18; Lymphocytes T; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Nuclear transport; Nucleotides; Oligomerization; onset; Pathogenesis; Proteins; Retina; Retinopathy; Statistical significance; Western blotting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214471

The aim of this study was to characterize the role of nucleotide-binding oligomerization domain- (NOD-) like receptor (NLR) protein 3 (NLRP3) inflammasome activation in the onset of diabetic retinopathy (DR) using retina and vitreous from donors without diabetes mellitus (CTL), with diabetes mellitus alone (DM), and with DR. Retinal expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), the key markers of retinal inflammation, connexin43 (Cx43) which is involved in upstream inflammasome regulation, as well as NLRP3 and cleaved caspase-1, the main markers of inflammasome activation, were evaluated using immunohistochemistry and Western blotting. Vitreous interleukin (IL)-1β and IL-18, biomarkers of the activated inflammasome, were measured using a Luminex multiplex assay. Results showed a significant increase in the number and size of Iba-1 cells and NLRP3 expression in DM, while a significant increase in GFAP, Cx43, cleaved caspase-1 and vitreous IL-18, as well as a further increase in Iba-1 and NLRP3 was found in DR. This suggests that the inflammasome is already primed in DM before its activation in DR. Furthermore, IL-18 may act as the major effector of inflammasome activation in DR while nuclear translocation of cleaved caspase-1 may play a role in gene transcription contributing to DR onset.