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Michelle C Callegan, Phillip S Coburn, Frederick Christian Miller, Austin L LaGrow, Craig Land, Yijie Chen, Weiwei Gao, Liangfang Zhang; Efficacy of Nanosponges in Protecting Retinal Function During Bacterial Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):500.
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© ARVO (1962-2015); The Authors (2016-present)
To compare the efficacy of biomimetic erythrocyte membrane encapsulated nanoparticles (nanosponges) in neutralizing pore-forming toxins (PFTs) in vitro and in protecting the retina during sterile and Gram-positive bacterial endophthalmitis.
Gram-positive ocular pathogens with known PFTs were tested: Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, and Streptococcus pneumoniae. In vitro: Nanosponges were generated from rabbit erythrocytes. Bacteria were cultured in growth media. The ability of nanosponges to neutralize PFTs secreted into this media were tested by microtiter hemolytic assays. In vivo sterile endophthalmitis: Bacteria were cultured in growth media. Resulting supernatants were filter sterilized and treated with nanosponges. Supernatants were centrifuged to remove nanosponges. 0.5 μl of nanosponge-treated supernatants were intravitreally injected into C57BL/6J mouse eyes (N=≥6/group). 24 h later, eyes were analyzed by ERG and harvested for histology. Bacterial endophthalmitis: 100-1000 CFU/0.5 μl (strain dependent) of each species were intravitreally injected into C57BL/6J mouse eyes (N=≥6/group). 6 h later, infected eyes were intravitreally injected (0.5-1.0 μl) with nanosponges alone (2 μg), gatifloxacin (Zymaxid) alone (1.25 μg), nanosponges + gatifloxacin, or were left untreated. At 24 h postinfection (or 12 h for B. cereus), eyes were analyzed by ERG and harvested for bacterial counts and histology.
Nanosponge pre-treatment of bacterial supernatants counteracted PFT activity. In vitro, this resulted in reduced hemoglobin release from erythrocytes. In sterile endophthalmitis, this resulted in significantly greater retinal function and, in general, less ocular pathology. In bacterial endophthalmitis, gatifloxacin and gatifloxacin + nanosponges significantly reduced intraocular bacterial burdens. However, reductions in retinal function loss afforded by gatifloxacin or gatifloxacin + nanosponges may not have been clinically significant.
While nanosponges were able to effectively reduce the toxic activities of PFTs against erythrocytes in vitro and during sterile endophthalmitis in vivo, their utility with or without gatifloxacin in active intraocular bacterial infections is less clear. Future studies will include optimizing the timing and dosage of nanosponges for the eye, as well as their efficacy with other ocular antibiotics during infection.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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