RESUMO
After successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of the epiretinal membrane, while effective treatment to prevent PVR is still unavailable. Therefore, we investigated the potential of doxycycline, an antibiotic in the tetracycline class, to treat PVR using a mouse model. We used the human retinal pigment epithelial cell line, ARPE-19, for in vitro and in vivo studies to test doxycycline for PVR treatment. We found that doxycycline suppressed the migration, proliferation, and contraction of ARPE-19 cells with reduced p38 MAPK activation and total MMP activity. Intravitreal doxycycline and topical tetracycline treatment significantly ameliorated the PVR severity induced by ARPE-19 cells in mice. PVR increased the expression of MMP-9 and IL-4 and p38 MAPK phosphorylation and modestly decreased IL-10. These effects were reversed by doxycycline and tetracycline treatment in the mouse retina. These results suggest that doxycycline will be a potential treatment for PVR in the future.
Assuntos
Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Vitreorretinopatia Proliferativa/tratamento farmacológico , Animais , Linhagem Celular , Quimiocina CXCL9/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Injeções Intravítreas , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Retina/efeitos dos fármacos , Retina/enzimologia , Vitreorretinopatia Proliferativa/metabolismo , Corpo Vítreo/efeitos dos fármacos , Corpo Vítreo/enzimologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PURPOSE: Postoperative endophthalmitis caused by nontuberculous mycobacterium is a rare but devastating complication after intraocular surgery. However, optimal treatment strategies remain undetermined in view of its rarity. METHODS: We investigated the cases of culture-proven postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis in southern Taiwan, focusing on clinical manifestations and microbiological study, and aimed to describe clinical staging and to propose a therapeutic modality for this disease. RESULTS: Twelve cases, including two published cases, were treated in two medical centers in southern Taiwan between Aug. 2011 and Dec. 2016, and all ever received cataract surgery at one clinic. Their disease courses could be categorized into four distinct stages, i.e., the initial, quiescent, recurrent, and end stage, and some cases experienced 1-4 cycles of quiescent-recurrent stages. Although all eyes ended up with phthisis or were eviscerated, the affected eyes receiving pars plana vitrectomy (PPV) tended to become quiescent and survived longer than those without PPV (adjusted hazard ratio: 13.9, p < 0.05). Eight isolates of eight patients were available for microbiological study. All isolates were susceptible to amikacin, and inducible clarithromycin resistance was observed in 100% of isolates. CONCLUSION: Despite the preservation of vision in postoperative M.abscessus endophthalmitis remained a challenge, a stage-based approach is proposed, which may facilitate decision-makings for the future study.