Intraocular Inflammasome Activation in Pseudophakic Bullous Keratopathy

Abstract

Purpose : High intraocular levels of proinflammatory cytokines have been associated with low corneal endothelial cell density in pseudophakic bullous keratopathy (PBK). However, it is unknown which mechanism is involved in this interaction. The adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) is part of the inflammasome, a protein complex responsible for triggering the activation of the pro-inflammatory cytokine IL-1β and the inflammasome-mediated cell death process of pyroptosis. In the present study, we measured the intraocular levels of ASC among patients with PBK and Fuchs’ dystrophy to assess the role of pyroptosis-mediated endothelial cell death and correlate them with clinical parameters such as central corneal thickness (CCT) and ocular surface inflammation.

Methods : Aqueous humor (AqH) samples from 17 patients were analyzed. These samples were collected at the beginning of surgery from patients with PBK (5) and Fuchs’ dystrophy (4) who underwent cornea transplantation, and healthy patients undergoing cataract surgery (8). The presence of the inflammasome was assessed by measuring ASC levels of the AqH samples via Simple Plex technology (Protein Simple). Additionally, a correlation between ASC concentrations and clinical parameters (CCT measured by ultrasound pachymetry and ocular surface inflammation measured by InflammaDry^® tear immunoassay) among the subjects was made.

Results : Protein levels of ASC were significantly higher in the AqH of patients with PBK compared with both Fuchs’ dystrophy [Mann-Whitney U, or Wilcoxon, (MWW) test p=0.016] and the control group (MWW test p=0.001). Fuchs’ dystrophy and controls did not show significance when compared to each other. Regarding clinical measurements, there was a positive correlation between the levels of ASC in AqH and the InflammaDry^® assay severity (Kendall’s tau correlation coefficient=0.55, p=0.020). Also, the CCT positively correlated with protein levels of ASC in the AqH (Spearman's rank correlation coefficient=0.53, p=0.028).

Conclusions : Significantly higher levels of ASC in the AqH of patients with PBK suggest that the inflammasome may play an important role in the disease and should be further studied for therapeutic purposes. Moreover, protein levels of ASC in the AqH could aid to a better management of the PBK patient population in combination with the parameters used during standard clinic visits.

This is a 2021 ARVO Annual Meeting abstract.