Sputum microRNA-screening reveals Prostaglandin EP3 receptor as selective target in allergen-specific immunotherapy.

BACKGROUND: Several microRNAs (miRs) have been described as potential biomarkers in liquid biopsies and in the context of allergic asthma, while therapeutic effects on the airway expression of miRs remain elusive. In this study, we investigated epigenetic miR-associated mechanisms in the sputum of grass pollen-allergic patients with and without allergen-specific immunotherapy (AIT). METHODS: Induced sputum samples of healthy controls (HC), AIT-treated and -untreated grass pollen-allergic rhinitis patients with (AA) and without asthma (AR) were profiled using miR microarray and whole-transcriptome microarray analysis of the same samples. miR targets were predicted in silico and used to identify inverse regulation. Local PGE2  levels were measured using ELISA. RESULTS: Two hundred and fifty nine miRs were upregulated in the sputum of AA patients compared with HC, while only one was downregulated. The inverse picture was observed in induced sputum of AIT-treated patients: while 21 miRs were downregulated, only 4 miRs were upregulated in asthmatics upon AIT. Of these 4 miRs, miR-3935 stood out, as its predicted target PTGER3, the prostaglandin EP3 receptor, was downregulated in treated AA patients compared with untreated. The levels of its ligand PGE2 in the sputum supernatants of these samples were increased in allergic patients, especially asthmatics, and downregulated after AIT. Finally, local PGE2  levels correlated with ILC2 frequencies, secreted sputum IL-13 levels, inflammatory cell load, sputum eosinophils and symptom burden. CONCLUSIONS: While profiling the sputum of allergic patients for novel miR expression patterns, we uncovered an association between miR-3935 and its predicted target gene, the prostaglandin E3 receptor, which might mediate AIT effects through suppression of the PGE2 -PTGER3 axis.

[Vasculitis of the retina : Clinical aspects, diagnostics, management and treatment]. / Vaskulitis der Retina : Klinik, Diagnostik, Management und Therapie.

Inflammatory changes in the retinal vessels can be attributed to a wide range of etiologies. These include infections, intraocular and systemic autoimmune processes, general diseases and iatrogenic factors. As the endothelium of the retinal capillaries forms the inner blood-retinal barrier, a disruption of this structure is directly associated with consequences for the fluid electrolyte balance of the retina. Clinical sequelae can include leakage of the retinal vessels and macular edema, which are often functionally threatening and significantly reduce the quality of life of patients. As the eye can be affected as an "index organ", a work-up of the patient by the ophthalmologist is of great importance. In the age of "precision medicine", efforts are being made to gain new insights into the pathogenetic mechanisms of vasculitis through "omics" in order to develop innovative treatment concepts.

Exploring Non-Modifiable and Modifiable Determinants of Vision-Related Quality of Life in Central Serous Chorioretinopathy.

Background: To longitudinally investigate the impact of best-corrected visual acuity (BCVA), non-modifiable risk factors, modifiable habits, and disease course on the vision-related quality of life (VRQOL) of patients with central serous chorioretinopathy (CSCR). Methods: We longitudinally enrolled 109 CSCR patients and 42 non-diseased control participants from our clinic. In addition to clinical examination, the National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) was employed for assessments, along with questions pertaining to various aspects of lifestyle habits. Alongside the cross-sectional analyses, the VRQOL of CSCR patients was tracked longitudinally over one year. Results: Consistent with prior studies, CSCR patients reported a lower VRQOL compared to non-diseased participants (79.3 ± 14.1 for CSCR and 92.6 ± 7.6 for CTRL; p < 0.0001), but fared better than those with other ocular conditions. No significant associations were observed between BCVA, any non-modifiable risk factors, or interventions, and VRQOL, both in cross-sectional and longitudinal contexts (cross-sectional BCVA with VRQOL: Pearson r correlation 0.173, p = 0.072). Among modifiable habits, sleep duration (p = 0.036), perceived quality of sleep rhythm (p = 0.006), hours of physical activity (p = 0.036), and the presence of non-ocular conditions (p = 0.001) were significantly correlated with VRQOL. Notably, enhanced sleep duration (+4.232 vs. -0.041 non-enhanced at 3 months, p = 0.033) and higher perceived quality of sleep rhythm (+6.248 vs. +0.094 non-higher, p = 0.009) showed a positive correlation with improved VRQOL over time. Conclusions: The study reveals that VRQOL has minimal dependence on BCVA or other clinical factors, suggesting that patient-reported outcome measures (PROMs) could serve as alternative endpoints in clinical studies for more holistic patient welfare assessment. Furthermore, the strong correlations between VRQOL and modifiable lifestyle habits indicate potential therapeutic value in targeting these areas for intervention.

[Noninfectious posterior uveitis : Clinical aspects, diagnostics, management and treatment]. / Nichtinfektiöse posteriore Uveitis : Klinik, Diagnostik, Management und Therapie.

Noninfectious posterior uveitis (NPU) comprises a heterogeneous group of vision-threatening, immune-mediated ocular and systemic diseases. It is predominantly bilateral and recurrent and, if not treated properly, leads to severe tissue damage that threatens the eyesight. In industrialized countries ca. 10-20% of all cases of blindness are caused by NPU. An NPU can occur at any age but is most common between the ages of 20 and 50 years. Laboratory diagnostic and imaging procedures enable an increasingly better differentiation of the disease spectrum. This makes it possible to better assess the course and prognosis of individual disease entities. An increasing repertoire of systemic and intravitreal forms of treatment has already led to more favorable long-term treatment outcomes. It can be expected that further progress can be achieved with better knowledge of the pathophysiology of the different clinical disorders and appropriate, targeted treatment.

A Comprehensive Update on Retinal Vasculitis: Etiologies, Manifestations and Treatments.

Retinal vasculitis is characterized by inflammatory involvement of retinal arterioles, venules and/or capillaries and can be associated with a myriad of systemic and ophthalmic diseases. In this review, we have comprehensively discussed the etiologies, clinical manifestations, and presentations of retinal vasculitis. We have also included newer advances in imaging in retinal vasculitis such as OCTA and widefield imaging.

Findings and Graduation of Sarcoidosis-Related Uveitis: A Single-Center Study.

Ocular involvement is present in up to 79% of sarcoid patients. Uveitis is the main ocular manifestation and presents as a chronic intraocular inflammatory condition with potentially detrimental effects on visual acuity and quality of life. This retrospective study was conducted to explore the incidence and characteristics of ocular sarcoidosis in a single tertiary ophthalmology center. Medical records of 84 patients presenting between June 2007 and March 2021 were analyzed. Based on the "International Workshop on Ocular Sarcoidosis" (IWOS) criteria, ocular sarcoidosis was determined as: definite (n = 24; 28.6%), presumed (n = 33; 39.3%), probable (n = 10; 11.9%), and indefinite (n = 17; 20.2%) in our study population. In 43.9% of the definite and presumed cases, the eye was primarily affected. In addition to specific ocular findings, the diagnosis was supported by biopsy (28.6%) and chest x-ray or computer tomography (66.7%). Moreover, an increased soluble interleukin-2 receptor (sIL-2R) expression (76.2%), elevated angiotensin-converting enzyme (ACE) levels (34.8%), and lymphocytopenia (35.1%) were valuable laboratory findings. Co-affected organs were lungs (60.7%), skin (15.5%), and central nervous system (8.3%). Our findings support the prominent role of the eye in the early detection of sarcoidosis. In addition to the IWOS criteria, sIL-2R, in particular, was shown to be relevant in establishing the diagnosis.