Abstract
Purpose :
Inflammation is a protective host response evoked during injury or microbial Infection. However, persistent inflammation can cause ocular tissue damage, warranting newer non-immunosuppressive anti-inflammatory therapeutic. In this study, we investigated the anti-inflammatory and adjunct therapeutic role of a bioactive lipid mediator, resolvin D1 (RvD1), in combination with antibiotics and steroids.
Methods :
Endophthalmitis was induced in wild type C57BL/6 mice via intravitreal injection of S. aureus. Six hours post-infection, eyes were treated with RvD1, sub-MIC levels of vancomycin, and dexamethasone either alone or in various combinations. Untreated eyes and eyes with PBS injection were used as controls. The disease progression was monitored via ophthalmoscopic examination, electroretinography (ERG), histopathological exam, and bacterial burden estimation. The level of intraocular inflammatory cytokines and chemokines was assessed by qPCR and ELISA.
Results :
Intravitreal injection of RvD1 either alone or in combination with vancomycin significantly improved the disease outcome as revealed by the drastically reduced bacterial burden, intraocular inflammatory cytokines (IL1β and IL-6), and chemokines (MIP2 and KC), and preserved ERG ‘a’ and ‘b’ wave response. Among the combination therapies, RvD1 + vancomycin exhibited better resolution of inflammation in comparison to the dexamethasone + vancomycin combination. Importantly, RvD1 treatment protected mice even with the sub-MIC levels of vancomycin, whereas dexamethasone failed to exert protection under these conditions. The histopathological analysis also revealed that RvD1 can protect retinal tissue architecture either alone or in combination with vancomycin.
Conclusions :
Our study demonstrates that RvD1 could be used as an adjunct therapy in combination with antibiotics to treat bacterial endophthalmitis. RvD1 therapy can also reduce the dosage of the overall antibiotics required to control bacterial proliferation in this devastating ocular complication.
This is a 2021 ARVO Annual Meeting abstract.