Purpose: To identify the risk factors for endogenous endophthalmitis secondary to Klebsiella pneumoniae liver abscess. Methods: We conducted a retrospective review of medical records of 602 patients admitted with K. pneumoniae liver abscess from January 1991 to November 2009. Variables included age, sex, history, month of onset, systemic condition, initial and final visual acuities, slit-lamp biomicroscopy, intraocular pressure, fundus, course and treatment. Results: Endophthalmitis was identified in 42 patients (53 eyes). Nineteen eyes (35.8%) had final vision of counting fingers or better. Diabetes was significantly associated with the development of endophthalmitis (P = 0.003) and poor visual outcome (P = 0.019). Poor initial vision (worse than counting fingers) was also significantly related to the poor visual outcome of endophthalmitis (P < 0.001). Subgroup analysis of 9 vitrectomy cases showed that progressive anterior chamber reaction might be related to poor visual outcome. Moreover, patients whose disease onset was in winter were slightly more likely to develop endophthalmitis (P = 0.088). Conclusion: Although the prognosis of endogenous K. pneumoniae endophthalmitis is generally poor, some eyes might be saved if treated early enough. Diabetes is a significant risk factor for the development of endogenous endophthalmitis and poor visual outcome in patients with K. pneumoniae liver abscess. Early vitrectomy might be considered in patients whose anterior chamber inflammation did not respond well to intravitreal antibiotics.
Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.
Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm2 for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24–48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light’s effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.
27 July 2016 in Ocular Immunology and Inflammation
Purpose: To analyze the patterns and etiologies of uveitis at a tertiary referral center in Taiwan. Methods: This retrospective chart review of uveitis patients from January 2001 to December 2014 updates a previous study a decade ago (2003). Results: We identified 450 patients, among whom anterior uveitis was most common, followed by panuveitis, posterior uveitis, and intermediate uveitis. A specific diagnosis was identified in 331 patients. In 73 infectious uveitis cases, herpetic anterior uveitis was the leading cause, followed by endogenous bacterial endophthalmitis and acute retinal necrosis. In 258 non-infectious uveitis cases, HLA-B27-associated uveitis was most commonly seen, followed by Vogt–Koyanagi–Harada disease and Posner–Schlossman syndrome. Compared with our previous study, we found more viral infection and sarcoidosis but fewer cases of Behçet disease, tuberculosis, and toxoplasmosis. Conclusions: Our results provide useful information about the patterns and etiologies of uveitis in a selected population in Taiwan.