Nottingham University Hospital and University of Nottingham, Nottingham NG7 2UH, UK. BMJ (online)
(Impact Factor: 17.45).
06/2013; 346(jun11 1):f3518. DOI: 10.1136/bmj.f3518
Available from: PubMed Central
- "Glaucoma is a chronic neurodegenerative disease . The progressive degeneration of retinal ganglion cells (RGCs) and sustained loss of the visual field are its remarkable characteristics . Recent studies suggested that activated microglia participate in the pathological course of glaucomatous optic injury with adverse consequences , , and reduced microglial activation was associated with alleviating optic nerve and retinal neurodegeneration . "
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ABSTRACT: Background and Objective
Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra Moore. Recent studies have suggested that TET can reduce the inflammatory response in microglia, but the mechanisms remain unclear. The aim of this study is to investigate whether TET can inhibit lipopolysaccharide (LPS)-induced microglial activation and clarify its possible mechanisms.
Study Design/Materials and Methods
Cell viability assays and cell apoptosis assays were used to determine the working concentrations of TET. Then, BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the mRNA or protein levels of IL1β and TNFα. Western blotting was utilized to quantify the expression of CD11b and cell signaling proteins.
TET at optimal concentrations (0.1 µM, 0.5 µM or 1 µM) did not affect the cell viability. After TET pretreatment, the levels of IL1β and TNFα (both in transcription and translation) were significantly inhibited in a dose-dependent manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK 1/2 expression were also suppressed by TET.
Our results indicate that TET can effectively suppress microglial activation and inhibit the production of IL1β and TNFα by regulating the NF-kB and ERK signaling pathways. Together with our previous studies, we suggest that TET would be a promising candidate to effectively suppress overactivated microglia and alleviate neurodegeneration in glaucoma.
Available from: Lital Keinan-Boker
- "In 2011, 2.71 million persons in the USA had POAG, with the highest estimated number among populations aged 70–79 years (2). In the UK, the National Health Service recently reported >1 million glaucoma-related visits per year (3). Early diagnosis and treatment of glaucoma has been found clinically beneficial and cost effective as it significantly delays visual field deterioration (4,5). "
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ABSTRACT: Background.Primary open-angle glaucoma is a leading cause of irreversible blindness.Objectives.To identify factors associated with adherence to glaucoma pharmacotherapy in the primary care setting, focusing on physicians’ role.Methods.Patients were recruited from primary care clinics and telephone-interviewed using a structured questionnaire that addressed patient-, medication-, environment- and physicians-related factors. Patients’ data on pharmacy claims were retrieved to calculate the medication possession ratio for measuring adherence.Results.Seven hundred thirty-eight glaucoma patients were interviewed. The multivariate analysis identified eight variables that were associated independently with adherence. Barriers to adherence were found to be low income, believing that ‘It makes no difference to my vision whether I take the drops or not’ and relying on someone else for drop instillation (exp(B) = 1.91, P = 0.002; exp(B) = 2.61, P < 0.0001; exp(B) = 2.17, P = 0.001, respectively). Older age, having a glaucoma patient among close acquaintances, taking a higher number of drops per day, taking a prostaglandin drug and reporting that the ophthalmologist had discussed the importance of taking eye drops as prescribed, were found to promote adherence (exp(B) = 0.96, P < 0.0001; exp(B) = 0.54, P = 0.014; exp(B) = 0.81, P = 0.001; exp(B) = 0.37, P < 0.0001; exp(B) = 0.60, P = 0.034, respectively). No association was found between the patient’s relationship with the family physician and adherence to glaucoma treatment.Conclusion.Adherence to glaucoma pharmacotherapy is associated with patient-related, medication-related, physician-related and environmental factors. Ophthalmologists have a significant role in promoting adherence. However, the potential role of family physicians is unfulfilled and unrecognized.
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