title: NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy.
abstract: OBJECTIVE
  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 (NLRP3) 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 NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR).
  
  
  METHODS
  Inflammasome components NLRP3 and caspase-1, inflammasome-related pro-inflammatory cytokines IL-1β 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 NLRP3 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-1β, TNF-α, IL-6, and IFN-γ that were detectable in the vitreous of both non-PDR and PDR patients.
  
  
  CONCLUSIONS
  Our results suggest that NLRP3 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.
authors.affiliation: Unit of Vitreoretinal Surgery, Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Sirpa
authors.identifier: http://orcid.org/0000-0002-2506-3900
authors.initials: S
authors.lastname: Loukovaara
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Piippo
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Kinnunen
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.|Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Hytti
authors.affiliation: Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.|Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D003930:Diabetic Retinopathy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D011446:Prospective Studies; D015398:Signal Transduction; D041623:Tomography, Optical Coherence / Q000379:methods*; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology*
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human
keywords: IL-18; NLRP3; diabetic retinopathy; inflammasome; inflammation; vitrectomy