Abstract
Purpose :
This study aimed to explore the therapeutic potential of OLT1177 (Dapansutrile), a specific inhibitor targeting the nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome, in an oxygen-induced retinopathy (OIR) mouse model.
Methods :
C57BL/6J newborn mice were randomly assigned to the normal control group, OLT1177 control group, OIR group, and OIR+OLT177 intervention group. The OIR model was established and a single intravitreal injection of OLT1177 (100μM) or saline was administered to mice on postnatal day 12 (P12). Various methods such as retinal flatmounts, immunofluorescence, Hematoxylin and Eosin staining and western blot were used to evaluate the safety of OLT1177 and its effects on retinal neovascularization of mice on P17.
Results :
OLT117 (100μM) has demonstrated high safety in maintaining both the normal retinal structure and vascular development. It was revealed that OLT1177 (100μM) significantly reduced the pathological neovascular area and central avascular area in OIR mice, which coincided with a decrease of endothelial cell nucleis penetrating the inner limiting membrane into the vitreous. Also, immunofluorescence suggested that OLT1177 effectively attenuated the aggregation and activation of microglial cells in the neovascular area of OIR mice, which was attributed to the inhibitory effect of OLT1177 on the activation of NLRP3 inflammasomes.
Conclusions :
OLT1177 exhibited a protective effect in the OIR mouse model by inhibiting the activation of microglial NLRP3 inflammasomes, which was potential as an alternative treatment for RNV.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.