부산대학교 도서관

Purpose: i/ To analyse the time course of retinal ganglion cell death (RGCs) after systemic injection of LPS in mice. ii/ To analyse the neuroprotective effect of P2X7 or TNFR1 receptor antagonism after LPS treatment. Methods: Male C57BL/6J mice were given an intraperitoneal injection of increasing doses of LPS and retinas were analysed at 3 days. Once the dose was set, to test the neuroprotective effect of the antagonism of the P2X7 and the TNFR1 receptors, antagonists were administered subcutaneously or intraperitoneally, alone or in combination. Control groups were intact animals and animals treated with LPS + vehicle. In all groups, retinas were dissected flat and the total number of RGCs immunodetected with Brn3a was quantified. Results: Significant death of RGCs was observed with doses higher than 4 mg/kg of LPS. In LPS treated animals, the loss of RGCs was observed at 3 days a progressed up to 7 days when 31% of the original RGC population was lost. From 7 to 21 days RGC loss did not progress. Antagonism of P2X7R or TNFR1 rescued 95% and 92% respectively of the original RGC population. Combination of both treatments did not improve each one alone. Conclusions: A single injection of LPS causes RGC death which is rescued by more than 90% by antagonizing the inflammasome or the extrinsic pathway of apoptosis. [ABSTRACT FROM AUTHOR]