Agonistic autoantibodies against β2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients

PURPOSE: Agonistic β2-adrenergic receptor autoantibodies (β2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the β2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to β2-agAAb status in patients with OAG. MATERIAL AND METHODS: Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of β2-agAAb. RESULTS: (I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the β2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028). CONCLUSION: FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of β2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that β2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A

Selenspiegel bei Glaukompatienten: eine Pilotstudie.

Hintergrund Spurenelemente können über oxidativen Stress vermittelte molekulare Interaktionen in die Pathogenese der Glaukomerkrankung eingreifen. Vor allem für das Spurenelement Selen (Se) wird eine Mitbeteiligung postuliert. Der Selengehalt im Serum wird unter anderem über die Ernährung gesteuert und unterliegt damit kulturellen und ethnischen Variabilitäten. Das Ziel der vorliegenden Studie war es, den Serumselenspiegel bei Patienten mit primärem Offenwinkelglaukom (pOWG) im Vergleich zu einer Kontrollgruppe zu analysieren. Diese Ergebnisse der vorliegenden deutschen Kohorte wurden auf mögliche Alters- und Gendereffekte hin untersucht sowie ins Verhältnis zu der bislang einzig beschriebenen Kohorte in den US gesetzt. Material und Methoden Die Selenkonzentration wurde von 39 Serumproben (22 pOWG, 17 Kontrollen) anhand der Inductively coupled Plasma-sector Field Mass Spectrometry (ICP-sf-MS) analysiert. Die statistische Analyse umfasste eine Kovarianz-, Perzentilenregressions-, Alters- und Genderanalyse. Ergebnisse Die Serumselenkonzentration (Ls-mean) betrug 134,86 µg/l für Patienten mit pOWG und 132,02 µg/l für die Kontrollgruppe. Der Serumselengehalt zwischen diesen beiden Gruppen zeigte keinen signifikanten Unterschied (p > 0,05). Jedoch war ein dezenter Alters- und Gendereffekt zu beobachten. Die Quantilanalyse erbrachte eine Reduktion der 1. Serumselenquantile mit ansteigendem Alter bei den Patienten mit pOWG im Gegensatz zu den Kontrollprobanden. Die Odds Ratio der 1. Quantile betrug 1,3 (jeweils in Bezug zur 2. und 3. Quantile). Zusammenfassung Der Serumselengehalt von Patienten mit pOWG zeigte sich als ca. halb so hoch wie der publizierte Wert der US-Literaturkohorte (Glaukom 209,11 ng/ml; Kontrolle 194,45 ng/ml). Zusätzlich war ein leichter Alters- und Gendereffekt zu beobachten

OCT angiography: Measurement of retinal macular microvasculature with spectralis II OCT angiography - reliability and reproducibility.

Aim: The aim of the present study was to investigate the reliability of macular microvasculature measurements in normal subjects by Heidelberg Spectralis II optical coherence tomography angiography (OCT-A) in combination with a newly made software. Subjects and Methods: This prospective study included 23 eyes of 23 persons from the Erlangen Glaucoma Registry (ISSN 2191-5008, CS-2011; NTC00494923). The subjects underwent a complete clinical, standardized ophthalmologic examination to rule out any eye disease. En face OCT-A imaging was done using Heidelberg Spectralis II OCT (Heidelberg, Germany). Images were recorded with a 15 x 15 degrees angle and a lateral resolution of 5.7 mu m/pixel, resulting in a retinal section of 2.9 x 2.9 mm. The Erlangen-Angio-Tool (EA-Tool) OCT-A application performed multiple segmentations, allowing analysis of the vessel density in 12 segments. The software was coded in MATLAB. Macular data on the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were exported into the application and analyzed separately. The EA-Tool calculated the percentage of "white area" in the "total area" of the region of interest, called vessel density. Foveolar avascular zones (FAZs) of the SVP, ICP, and DCP were calculated manually. To investigate the reproducibility of the new software, individual scans (SVP, ICP, and DCP) were analyzed twice with the EA-Tool and intraclass coefficients (ICCs) of the vessel density values were calculated. Statistical analysis was performed with SPSS version 21.0. Results: The mean vessel density of the SVP ranged between 30.4 and 33.5, that of the ICP between 20.9 and 24.7, and that of the DCP between 23.5 and 27.6. Bland-Altman plots showed a good reliability of two consecutive scans of each sector (S1-S12) in the SVP, ICP, and DCP. Testing reproducibility, no statistically significantly different sectorial coefficients of variation of the SVP, ICP, and DCP were observed (p > 0.05). The mean FAZ area of the SVP was 0.43 +/- 0.16 mm(2), that of the ICP 0.28 +/- 0.1 mm(2), and that of the DCP 0.44 +/- 0.12 mm(2). Conclusions: Spectralis OCT II, in combination with the semiautomated vessel density software EA-Tool, showed good or even excellent ICCs in 75% of all segments of the SVP, ICP, and DCP. The ICCs for the FAZ area in the SVP, ICP, and DCP were excellent

Meleagrin from marine fungus Emericella dentata Nq45: crystal structure and diverse biological activity studies.

Hamed A, Abdel-Razek AS, Araby M, et al. Meleagrin from marine fungus Emericella dentata Nq45: crystal structure and diverse biological activity studies. Natural product research. 2020:1-9.The crystal structure and unambiguous absolute configuration of meleagrin (1) isolated from fungus Emericella dentata Nq45 is reported herein to first time on the bases of single crystal X-ray diffraction. Together with 1, haenamindole (2), isorugulosuvine (3), secalonic acid D (4), ergosterol (5) and cerebroside A (6) were obtained and their structures were determined by ESI MS and NMR data analysis. Diverse biological activity of meleagrin (1) was investigated. Compound 1 pronounced potent cytotoxicity against the human cervix carcinoma cell line KB-3-1 and its multidrug resistant sub-clone KB-V1 of IC50 3.07 and 6.07M, respectively, in comparison with the reference (+) - griseofulvin (IC50 19, 19.5M). Based on the antibiofilm activity, compound 1 displayed as well potent activity against Staphylococcus aureus with an MIC of 0.25mg/mL. Isolation of the producing fungus and taxonomical characterization is stated as well

Terretonin O: a new meroterpenoid from Aspergillus terreus.

Hamed A, Abdel-Razek AS, Omran DA, et al. Terretonin O: a new meroterpenoid from Aspergillus terreus. Natural product research. 2019:1-10