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NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy
Author(s) -
Loukovaara Sirpa,
Piippo Niina,
Kinnunen Kati,
Hytti Maria,
Kaarniranta Kai,
Kauppinen Anu
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.13427
Subject(s) - inflammasome , pyrin domain , diabetic retinopathy , medicine , caspase 1 , immunology , cytokine , diabetes mellitus , inflammation , endocrinology
Purpose Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide‐binding domain and Leucine‐rich repeat Receptor containing a Pyrin domain 3 ( NLRP 3) inflammasomes are pro‐inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP 3 activation occurs in patients with sight‐threatening forms of diabetic retinopathy ( DR ). Methods Inflammasome components NLRP 3 and caspase‐1, inflammasome‐related pro‐inflammatory cytokines IL ‐1 β and IL ‐18, vascular endothelial growth factor ( VEGF ), acute‐phase cytokines TNF ‐ α and IL ‐6, as well as adaptive immunity‐related cytokine interferon gamma ( IFN ‐ γ ) were measured from the vitreous samples of 15 non‐proliferative diabetic retinopathy (non‐ PDR ) and 23 proliferative diabetic retinopathy (PDR) patients using the enzyme‐linked immunosorbent assay ( ELISA ) method. The adaptor protein apoptosis‐associated speck‐like protein containing a CARD (ASC) was determined using the Western blot technique. Results Inflammasome components were present in the vitreous of DR patients. Along with VEGF , the levels of caspase‐1 and IL ‐18 were significantly increased, especially in PDR eyes. Interestingly, clearly higher levels of NLRP 3 were found in the PDR eyes with tractional retinal detachment ( TRD ) than from PDR eyes with fully attached retina. There were no significant differences in the amounts of IL ‐1 β , TNF ‐ α , IL ‐6, and IFN ‐ γ that were detectable in the vitreous of both non‐ PDR and PDR patients. Conclusion Our results suggest that NLRP 3 inflammasome activation can be associated especially with the pathogenesis of PDR . The lack of differences in TNF ‐ α , IL ‐6, and IFN ‐ γ also alludes that acute inflammation or T‐cell‐mediated responses do not dominate in PDR pathogenesis.