Intracellular Thiol Redox Status Regulates Lymphangiogenesis and Dictates Corneal Limbal Graft Survival

Purpose.: Compounds regulating intracellular thiol redox status, such as N,N-diacetyl-L-cystine dimethylester (NM2), were shown to prolong corneal graft survival in a penetrating keratoplasty (PKP) model. However, the effect of NM2 on hemangiogenesis and lymphangiogenesis has not been investigated. The effect of manipulating ambient thiol redox status on riskier (higher rejection rate) transplantation models, such as limbal graft survival and hemangiogenesis and lymphangiogenesis in a corneal suture model, were investigated. Methods.: C57BL/10 mice that received BALB/c corneas were treated by subconjunctival injection of NM2, and limbal graft survival was assessed. Sutured C57BL/6 received daily intraperitoneal injections of NM2, glutathione diethylester (GSH-OEt), or PBS. Lymphatic endothelial cell (LEC) and peritoneal mps were treated with NM2 or GSHOEt, and then VEGFR3, neuropilin-2, podoplanin, and LYVE-1 expression were analyzed. Supernatants were collected for analysis of TNF-α and VEGF-A levels by ELISA. Results.: Significantly less cellular infiltration was detected in mice with corneal limbal transplant–treated NM2-treated mice. Hemangiogenesis and lymphangiogenesis were suppressed in the NM2-treated mice. NM2 treatment of mps led to reduced levels of VEGFR3, neuropilin-2, podoplanin, and LYVE-1 expression compared with PBS- or GSHOEt- treated mps, lower levels of TNF-α, and increased secretion of VEGF. Moreover, NM2-treated LECs had reduced levels of LYVE-1 and Prox-1. Conclusions.: Reduction of ambient redox status reduced inflammatory cell infiltrates. Consequently, reduced inflammatory response might have contributed to both the observed prolonged corneal limbal graft survival and the attenuated hemangiogenesis and lymphangiogenesis in cornea

The trend of resistance to antibiotics for ocular infection of Staphylococcus aureus, coagulase-negative staphylococci, and Corynebacterium compared with 10-years previous: A retrospective observational study.

OBJECTIVE:To retrospectively identify epidemiological trends of infection on the ocular surface and investigate trends of resistance to bacterial antibiotics compared with 10-years previous for Staphylococcus aureus, coagulase-negative staphylococci (CNS), and Corynebacterium in Japan. MATERIALS AND METHODS:Bacterial isolate samples were collected from the conjunctival sacs of eyes afflicted with conjunctivitis, keratitis, dacryocystitis, and hordeolum from September 2004 through November 2005 (n = 145 isolates) and September 2014 through November 2015 (n = 195 isolates) at the Baptist Eye Institute, Kyoto, Japan. The prevalence of methicillin-resistant S. aureus (MRSA), methicillin-resistant CNS (MR-CNS), and fluoroquinolone-resistant Corynebacterium were examined, and susceptibility of isolated bacteria to levofloxacin (LVFX), cefmenoxime (CMX), chloramphenicol (CP), erythromycin (EM), vancomycin (VCM), and arbekacin (ABK) were compared between both time periods using the disc susceptibility method. RESULTS:Over the 10-year period from initial to final examination, the prevalence of MRSA and MR-CNS significantly decreased from 52% to 22% (P < 0.05) and from 47% to 25% (P < 0.05), respectively, yet there was no change in the prevalence of fluoroquinolone-resistant Corynebacterium (60% and 54%; P = 0.38). Antibiotic-resistance trend analysis revealed that susceptibility to antibiotics in 2014-2015 was similar to that in 2004-2005. MRSA and MR-CNS were susceptible to CP (88%), VCM (100%), and ABK (100%), while fluoroquinolone-resistant Corynebacterium was susceptible to CMX (100%), VCM (100%), and ABK (96%). CONCLUSION:The prevalence of MRSA and MR-CNS significantly decreased between the two time periods, yet more than 50% of the Corynebacterium isolates were still resistant to LVFX. Although no increase in bacterial resistance to antibiotics was found, a cautionary use of fluoroquinolone eye drops should be considered

Sudden infant death due to mechanical asphyxia caused by a cervical ectopic thymus—An autopsy case

The 7-month-old girl was left in a nursery until following morning. About 3 h after being given milk, she was found dead in a right lateral supine position. There was no external evidence of injury to suggest a maltreatment. Hemorrhages were present in the accessory respiratory muscles, but the most notable findings were masses on either side of the trachea and immediately inferior to the thyroid gland. Both of masses were in continuity with the intrathoracic thymus. Histopathologically, the masses showed normal thymic structure and collagen fibers on the left side of the trachea showed metachromasia on Masson’s staining. There were no remarkable findings in organs except for congestion. The cause of death was determined to be mechanical asphyxia due to tracheal compression by the cervical ectopic thymus. Hemorrhage in the accessory respiratory muscle was considered to be caused by effortful breathing during the process of asphyxia. The metachromasia of Masson's stain on the trachea may be due to the same mechanism as a “compression mark reaction”, and may be useful in proving compression by the ectopic thymus. We consider that chronic compression of the trachea led to the tracheomalacia, which enabled the final lethal compression when lying in a right lateral supine position. An ectopic thymus is caused by a failure of descent of the embryonic thymic tissue into the thoracic cavity at the appropriate developmental stage and is generally asymptomatic. However, the cervical ectopic thymus should be considered in the diagnosis of a cause of sudden infant death