CTLA-4 is a negative regulator of T-cell activation, and its inhibitory effects can be accomplished either by competition with CD28 or by transmitting negative signals through its intracellular domain. To utilize the cytoplasmic domain of CTLA-4 to suppress allergic inflammation, we fused it to a novel protein-transduction domain in the human transcriptional factor Hph-1. Transduction efficiency was verified in vitro and in vivo after ocular, intranasal and intradermal administration. After transduction into T cells, the Hph-1-ctCTLA-4 fusion protein inhibited the production of interleukin (IL)-2, and downregulated CD69 and CD25. Intranasal administration of Hph-1-ctCTLA-4 resulted in markedly reduced infiltration of inflammatory cells, secretion of T helper type 2 (T(H)2) cytokines, serum IgE levels and airway hyper-responsiveness in a mouse model of allergic airway inflammation. These results indicated that Hph-1-ctCTLA-4 constitutes an effective immunosuppressive protein drug for potential use in the treatment of allergic asthma, via nasal administration.
Similar to the findings of previous East Asian studies, this study showed that Klebsiella pneumoniae was the most common causative organism of endogenous endophthalmitis and liver abscess was the most common infection focus. Although endogenous endophthalmitis is generally associated with poor visual acuity outcomes, the prognosis depends mainly on the initial visual acuity and the pathogen.
An eye with the more demonstrable structural deterioration, as shown by reduced RNFL thickness and GCC area, and retinal ganglion cell dysfunction as shown by decreased PhNR/b-wave amplitude ratio was associated with the worse visual fields outcome. RNFL thickness and GCC area measurements using OCT and PhNR/b-wave amplitude ratio could be a useful prognostic indicator in the preoperative assessment of chiasmal compression.
Visual field recovery and changes of RGCs after chiasmal decompression have similar aspects and are significantly correlated. However, prolonged retrograde degeneration progressed for some period, even after surgical decompression and visual field recovery preceded demonstrable retinal regeneration.
We aimed to investigate the risks of Alzheimer’s (AD) and Parkinson’s disease (PD) in the 10 years following diagnosis of open-angle glaucoma (OAG) using a nationwide cohort. This propensity score-matched retrospective cohort study included 1,025,340 subjects from the Korean National Health Insurance Service National Sample Cohort database. The OAG group (n = 1,469) included patients who were initially diagnosed with OAG between 2004 and 2007, and the subjects in the comparison group were matched in a 1:5 ratio using propensity scores. Cox regression analyses were performed to investigate the risks of developing AD or PD. The diagnosis of OAG was significantly associated with an increased incidence of AD (hazard ratio [HR] = 1.403, 95% confidence interval [CI] 1.180–1.669, p < 0.001), but not PD (HR = 0.995, 95% CI 0.620–1.595, p = 0.983) after adjusting for possible confounding factors. In subgroup analyses, participants with OAG aged ≥65 years were more likely to develop AD compared with those aged <65 years, and female OAG patients had a greater risk of developing AD than males. Patients diagnosed with OAG have a higher risk of developing AD, but not PD, and the risk differed according to age and sex.
Choroidal neovascularization (CNV) is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD) and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF), the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR) has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA), which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA) after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV) delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV.
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