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Joaquin Tosi, Pawan K Singh, Ashok Kumar; Effect of Enzymatic Vitreolysis with Plasmin on Intravitreal Antibiotics Therapy in a Mouse Model of Staphylococcal Endophthalmitis.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2874.
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Bacterial endophthalmitis is a serious complication of ocular surgeries and its current treatment involves intravitreal injections of antibiotics. Microplasmin has been shown to induce a posterior vitreous detachment (PVD) and vitreous liquefaction. In this study, using a mouse model of staphylococcal endophthalmitis, we tested the hypothesis that intravitreal injection of plasmin will enhance the diffusion of antibiotics, resulting in better killing of bacteria.
PVD was induced by injecting one microliter of plasmin (1 unit/µL) in the vitreous cavity of the right eyes of C57BL/6 mice (n=20), fellow eyes received one µL of saline and were used as controls. After 4 days, we assessed PVD and endophthalmitis was induced by injecting one microliter intravitreally containing 5000 colony forming units (CFUs) of GFP expressing S. aureus (strain RN6390/AL1757) in sterile PBS. After 6 h., various doses (0.5, 1, 5 µg/eye) of vancomycin were injected in the vitreous cavity of infected eyes with and without prior plasmin injection. 24 h. after antibiotic treatment, eyes were enucleated and subjected to histological analysis. In another experimental group, the eyes were subjected to bacterial counting, and retinal lysates were used for cytokine analysis.
Microscopic evaluation of the eyes injected with plasmin showed complete PVD after 4 days. The eyes treated with plasmin exhibited reduced pathology following antibiotics therapy compared to the eyes given antibiotics alone. Similarly, the bacterial burden and the levels of inflammatory cytokines were significantly lower in plasmin treated eyes. Moreover, plasmin treatment reduced the amount of antibiotics required to clear the pathogen. Our toxicity data revealed that intravitreal injection of plasmin does not causes any adverse effects on the mouse retina.
Plasmin may be a useful adjunct therapy for intravitreal delivery of antibiotics in the management of bacterial endophthalmitis. These results may have significant implications in the management of bacterial endophthalmitis in humans.
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