Novel Optical Imaging Probe for the Targeted Visualization of NLRP3 Inflammasomes in Living Retina

Activation of the
NLR-family pyrin domain-containing 3 (NLRP3)
inflammasome has been associated with diabetic retinopathy progression.
We have synthesized a highly sensitive molecular imaging probe, InflammaProbe-2,
as an early detection diagnostic tool for the in vivo molecular imaging
of NLRP3 inflammasomes in living diabetic retina. The ability of InflammaProbe-2
for the targeted visualization of the NLRP3 inflammasome was assessed
using an enzyme-linked immunosorbent assay (ELISA) by comparing its
ability to inhibit the NLRP3-mediated secretion of IL-1β. InflammaProbe-2
was able to visualize NLRP3 inflammasomes in ARPE-19 cells treated
under hyperglycemia as well as inflammatory conditions. Furthermore,
InflammaProbe-2-dependent in vivo and ex vivo imaging of the NLRP3
inflammasome was achieved via fluorescence enhancement in streptozotocin
(STZ)-induced diabetic retinopathy. In addition, the toxicity of InflammaProbe-2
was assessed in vitro and in vivo studies. InflammaProbe-2 showed
no significant changes in the a-wave and b-wave amplitudes of their
electrical response to flashes of light.