Abstract
Purpose :
To evaluate the toxic and inflammatory effects of moxifloxacin, cefuroxime, and vancomycin on human retinal vascular endothelial cells and pericytes in vitro, and in vivo.
Methods :
Primary human retinal vascular endothelial cells (HRVEC) and pericytes were exposed to moxifloxacin (MFLX), cefuroxime (CXM), and vancomycin (VCM). Adverse effect on cell viability was assessed using reduction of intrinsic esterase activity, kinetic cell viability and membrane damage. Inflammatory effect of these antibiotics was assessed by interleukin-8 (IL-8) and interleukin-1β (IL-1β) secretion. In vivo toxicities were examined using live/dead assay of intravitreally injected mice eyes.
Results :
Membrane damage and reduction of esterase activity induced by 24 h exposure of antibiotics was most notable for MFLX, and HRVEC was more susceptible than pericytes (HRVEC ≥125 μg/mL and Pericyte≥ 1000μg/mL). CXM also induced cell toxicity to HRVEC and pericytes, but loss of viability was lower than MFLX. VCM induced minimal cell toxicity. Kinetic cell viability assay showed that MFLX exposure at 500 μg/mL induced significant loss of viability as early as 1 h in HRVEC, and 50% survival time was 18 hours. MFLX showed similar kinetic toxicity to pericytes. When inflammatory effect of antibiotics was examined, significant induction of IL-8 was observed especially for HRVEC. CXM and VCM induced significant IL-8 secretion (CXM: 9784 pg / ml at 125 μg / ml, P <0.0001, VCM: 3104pg / ml at 500 μg / ml, P<0.0044). Pericytes showed significantly reduced IL-8 secretion by antibiotics (CXM: 10.7pg / ml at 1000 μg / ml, VCM: 9.753pg / ml at 500 μg / ml). For both of HRVEC and pericytes, IL-1β induction was minimal.
Intravitreal injection of antibiotics induced cell damage to retinal vascular endothelial cells at 12h. CXM and VCM showed more extended cell damage to inner nuclear layer cells.
Conclusions :
MFLX causes immediate damage to retinal vascular cells and pericytes, while CXM and VCM causes significant inflammatory effect. Surgeons need to be cautious of toxicity of prophylactic use of antibiotics, especially via intravitreal administration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.