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[Low-dose, long-term fumaric acidity esters within recalcitrant cutaneous sarcoidosis : Report regarding two cases].
1% versus 7.9%, p = 8.629e-09). Among 26 candidate genes, the prevalence rate of PDVs in five genes showed a statistically significant difference between patients and controls (33 out of 235 versus 1 out of 241, p = 4.533e-10), including ATXN2 (p = 0.0033), TXNRD2 (p = 0.0190), MYOC (p = 0.0140), FOXC1 (p = 0.0140), and CDKN2B (p = 0.0287). Furthermore, two sisters harboring a stop-loss mutation EFEMP1 p.Ter494Glu were found in the POAG cohort, and further analysis of the family strongly suggested that EFEMP1 p.Ter494Glu was a potentially disease-causing mutation for POAG. A statistically significant difference in age at diagnosis between patients with PDVs and those without PDVs was found, implying that some of the identified PDVs may have a role in promoting the early onset of POAG disease. Conclusions The results suggest that some of the associations identified in POAG risk loci can be ascribed to rare coding variants with likely functional effects that modify POAG risk.Purpose Risk for age-related macular degeneration (AMD), a slowly progressing, complex disease, is tied to an overactive complement system. Efforts are under way to develop an anticomplement-based treatment to be delivered locally or systemically. We developed an alternative pathway (AP) inhibitor fusion protein consisting of a complement receptor-2 fragment linked to the inhibitory domain of factor H (CR2-fH), which reduces the size of mouse choroidal neovascularization (CNV) when delivered locally or systemically. Specifically, we confirmed that ARPE-19 cells genetically engineered to produce CR2-fH reduce CNV lesion size when encapsulated and placed intravitreally. We extend this observation by delivering the encapsulated cells systemically in Matrigel. Methods ARPE-19 cells were generated to stably express CR2 or CR2-fH, microencapsulated using sodium alginate, and injected subcutaneously in Matrigel into 2-month-old C57BL/6J mice. Four weeks after implantation, CNV was induced using argon laser photocoagulation. Progression of CNV was analyzed using optical coherence tomography. Bioavailability of CR2-fH was evaluated in Matrigel plugs with immunohistochemistry, as well as in ocular tissue with dot blots. Efficacy as an AP inhibitor was confirmed with protein chemistry. Results An efficacious number of implanted capsules to reduce CNV was identified. Expression of the fusion protein systemically did not elicit an immune response. Bioavailability studies showed that CR2-fH was present in the RPE/choroid fractions of the treated mice, and reduced CNV-associated ocular complement activation. Conclusions These findings indicate that systemic production of the AP inhibitor CR2-fH can reduce CNV in the mouse model.Purpose To explore the correlation of tear and conjunctival cytokines and sensory hypersensitivity in mild dry eye (MDE) patients characterized by symptoms outweighing signs (DESOS). Methods The subjects comprised 39 patients with MDE characterized by DESOS, 18 patients with common MDE (CMDE), and 15 healthy controls. The patients with DESOS were randomly subdivided into two groups; the C-DESOS group received artificial tears only, and the G-DESOS group received artificial tears and 0.1% fluorometholone eye drops three times a day. Symptoms were assessed using the Ocular Surface Disease Index (OSDI) and the Neuropathic Pain Symptoms Inventory modified for Eye (NPSI-E) questionnaire. Ocular examinations and in vivo confocal microscopy (IVCM) were also employed. Tear and conjunctival cytokines were measured using Multiplex or RT-PCR on Days 0, 7, and 30. The correlation between the expression of cytokines and hypersensitivity status was analyzed. Results Compared with the CMDE and control groups, the DESOS groups showed a significant increase in symptom scores and in the ratio of symptoms versus signs. GSK2795039 molecular weight IL-1 β, IL-2, IL-6, and TNF-α in tears and conjunctiva increased in the DESOS groups compared to the CMDE and control groups, indicating a high correlation with hypersensitivity status in the DESOS groups. Glucocorticoid treatment significantly decreased the level of cytokines in tears and conjunctiva in the G-DESOS group and subsequently ameliorated the symptoms. Conclusions Tear and conjunctival cytokines, including IL-1 β, IL-2, IL-6, and TNF-α, were correlated with sensory hypersensitivity status in the DESOS groups, suggesting they play an important role in the discordance of symptoms outweighing signs.Despite decades of research, diabetic retinopathy remains the leading cause of blindness in working age adults. Treatments for early phases for the disease remain elusive. One pathway that appears to regulate neuronal, vascular, and inflammatory components of diabetic retinopathy is the cyclic adenosine 3', 5'-monophosphate (cAMP) pathway. In this review, we discuss the current literature on cAMP actions on the retina, with a focus on neurovascular changes commonly associated with preproliferative diabetic retinopathy models.Purpose North Carolina macular dystrophy (NCMD) is an autosomal dominant maculopathy that is considered a non-progressive developmental disorder with variable expressivity. Our study aimed to clinically and genetically characterize macular dystrophy in a family (MOL1154) consisting of six affected subjects with a highly variable maculopathy phenotype in which no correlation between age and severity exists. Methods Clinical characterization included visual acuity testing and electroretinography. Genetic analysis included Sanger sequencing and whole exome sequencing (WES). Results WES analysis performed on DNA samples from two individuals revealed a heterozygous deletion of six nucleotides [c.2247_2252del; p.(Leu750_Lys751del)] in the CFH gene. Co-segregation analysis revealed that five of the six NCMD affected subjects carried this deletion, while one individual who had a relatively mild phenotype compatible with dry age-related macular degeneration (AMD) did not carry it. We subsequently analyzed the upstream region of PRDM13 that has previously been reported to be associated with NCMD and identified a unique heterozygous transversion (chr6100040974A>C) located within the previously described suspected control region in all six affected individuals. This transversion is likely to cause NCMD. Conclusions NCMD has a wide spectrum of clinical phenotypes that can overlap with AMD, making it challenging to correctly diagnose affected individuals and family members. The DNA sequence variant we found in the CFH gene of some of the affected family members may suggest some role as a modifier gene. However, this variant still does not explain the huge phenotypic variability of NCMD and needs to be studied in other and larger populations.
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