55 research outputs found

    Radiation-pressure cooling and optomechanical instability of a micro-mirror

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    Recent experimental progress in table-top experiments or gravitational-wave interferometers has enlightened the unique displacement sensitivity offered by optical interferometry. As the mirrors move in response to radiation pressure, higher power operation, though crucial for further sensitivity enhancement, will however increase quantum effects of radiation pressure, or even jeopardize the stable operation of the detuned cavities proposed for next-generation interferometers. The appearance of such optomechanical instabilities is the result of the nonlinear interplay between the motion of the mirrors and the optical field dynamics. In a detuned cavity indeed, the displacements of the mirror are coupled to intensity fluctuations, which modifies the effective dynamics of the mirror. Such "optical spring" effects have already been demonstrated on the mechanical damping of an electromagnetic waveguide with a moving wall, on the resonance frequency of a specially designed flexure oscillator, and through the optomechanical instability of a silica micro-toroidal resonator. We present here an experiment where a micro-mechanical resonator is used as a mirror in a very high-finesse optical cavity and its displacements monitored with an unprecedented sensitivity. By detuning the cavity, we have observed a drastic cooling of the micro-resonator by intracavity radiation pressure, down to an effective temperature of 10 K. We have also obtained an efficient heating for an opposite detuning, up to the observation of a radiation-pressure induced instability of the resonator. Further experimental progress and cryogenic operation may lead to the experimental observation of the quantum ground state of a mechanical resonator, either by passive or active cooling techniques

    Inhibitory and agonistic autoantibodies directed against the ß(2)-adrenergic receptor in pseudoexfoliation syndrome and glaucoma

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    Pseudoexfoliation syndrome (PEXS) and glaucoma (PEXG) are assumed to be caused by a generalized elastosis leading to the accumulation of PEX material in ocular as well as in extraocular tissues. The exact pathophysiology of PEXS is still elusive. PEXG, the most common type of secondary open-angle glaucoma (OAG), is characterized by large peaks of intraocular pressure (IOP) with a progressive loss of the visual field. Agonistic autoantibodies (agAAbs) against the ß(2)-adrenergic receptor (AR) have been shown to be present in sera of patients with primary and secondary OAG and ocular hypertension and are seemingly linked to IOP. In the present study, we investigated the autoantibodies directed against the ß(2)-AR in sera of patients with PEXS and PEXG. We recruited 15, 10, and 15 patients with PEXG, PEXS, and primary OAG, respectively. Ten healthy individuals served as controls. All patients underwent standard ophthalmological examination with Octopus G1 perimetry. agAAbs prepared from serum samples were analyzed in a rat cardiomyocyte–based bioassay for the presence of agAAbs. We identified the interacting loop of the ß(2)-AR and the immunoglobulin G (IgG) subclasses using synthetic peptides corresponding to the extracellular loops of the receptors and enzyme-linked immunosorbent assay, respectively. None of the controls were ß(2)-agAAb–positive (0.2 ± 0.5 U). No ß(2)-agAAbs (0.2 ± 0.4 U), but inhibitory ß(2)-AAbs were observed in 80% of the patients that partially blocked the drug-induced ß(2)-adrenergic stimulation; 5.8 ± 1.7 U vs. 11.1 ± 0.9 U for clenbuterol in the absence and the presence of sera from patients with PEXS, respectively. Epitope analyses identified the third extracellular loop of the ß(2)-AR as the target of the inhibitory ß(2)-AAbs, being of IgG3 subtype in PEXS patients. In contrast, patients with PEXG showed ß(2)-agAAbs (5.6 ± 0.9 U), but no inhibitory ones. The ß(2)-agAAbs levels of patients with PEXG and primary OAG patients (3.9 ± 2.8 U; p > 0.05) were at a similar level. In two cases of PEXG, the ß(2)-agAAbs exert synergistic effects with clenbuterol. The activity increased from 11.5 ± 0.3 (clenbuterol only) to 16.3 ± 0.9 U. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma, agonistic and inhibitory ß(2)-AAbs seem to be a part of this multifactorial interplay

    Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms

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    Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies ((f)AABs) targeting G-protein coupled receptors (GPCR-(f)AABs) has been discussed to be involved. We, therefore investigated, whether GPCR-(f)AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-(f)AABs that acted as receptor agonists. Some of those GPCR-(f)AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-(f)AAB detection). Other GPCR-(f)AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-(f)AABs identified in the blood of Long-COVID patients targeted the β(2)-adrenoceptor (β(2)-(f)AAB), the α1-adrenoceptor (α(1)-(f)AAB), the angiotensin II AT1-receptor (AT1-(f)AAB), and the nociceptin-like opioid receptor (NOC-(f)AAB). The negative chronotropic GPCR-(f)AABs identified targeted the muscarinic M(2)-receptor (M(2)-(f)AAB), the MAS-receptor (MAS-(f)AAB), and the ETA-receptor (ETA-(f)AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies

    Agonistic β2-adrenergic receptor autoantibodies characterize the aqueous humor of patients with primary and secondary open-angle glaucoma

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    PURPOSE: Agonistic β2-adrenergic receptor autoantibodies (β2-agAAbs) were recently observed in sera of patients with ocular hypertension (OHT), primary (POAG), and secondary open-angle glaucoma (SOAG), yet not in healthy controls (HCs). It was the aim of the present study to investigate the presence of β2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding β2-agAAb serum data. MATERIAL AND METHODS: Thirty-nine patients (21 male, 18 female) were recruited from the Department of Ophthalmology, University of Erlangen-Nürnberg: twenty-one POAG, 18 SOAG. Aqueous humor samples were collected during minimal invasive glaucoma surgery. Serum and AH samples were analyzed for β2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U). RESULTS: Thirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a β2-agAAb in their sera and AH samples, respectively. All β2-agAAb AH-positive OAG patients were also seropositive. We also observed a β2-agAAb seropositivity in 95 and 89% of patients with POAG and SOAG, respectively. Beta2-agAAbs were seen in 86% (POAG) and 78% (SOAG) of AH samples. The β2-agAAb adrenergic activity was increased in the AH of patients with POAG (6.5 ± 1.5 U) when compared with those with SOAG (4.1 ± 1.1 U; p = 0.004). Serum β2-agAAb adrenergic activity did not differ between the cohorts [POAG (4.5 ± 1.5 U); SOAG (4.6 ± 2.1 U; p=0.458)]. No correlation of the beating rates were observed between serum and AH samples for group and subgroup analyses. CONCLUSION: The detection of β2-agAAb in systemic and local circulations supports the hypothesis of a direct functional impact of these agAAbs on ocular G-protein coupled receptors. The high prevalence of β2-agAAb in serum and AH samples of patients with POAG or SOAG suggests a common role of these AAbs in the etiopathogenesis of glaucoma, independent of open-angle glaucoma subtype

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

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    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

    How accurate is an LCD screen version of the Pelli–Robson test?

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    Purpose: To evaluate the accuracy and repeatability of a computer-generated Pelli–Robson test displayed on liquid crystal display (LCD) systems compared to a standard Pelli–Robson chart. Methods: Two different randomized crossover experiments were carried out for two different LCD systems for 32 subjects: 6 females and 10 males (40.5 ± 13.0 years) and 9 females and 7 males (27.8 ± 12.2 years), respectively, in the first and second experiment. Two repeated measurements were taken with the printed Pelli–Robson test and with the LCDs at 1 and 3 m. To test LCD reliability, measurements were repeated after 1 week. Results: In Experiment 1, contrast sensitivity (CS) measured with LCD1 resulted significantly higher than Pelli–Robson both at 1 and at 3 m of about 0.20 log 1/C in both eyes (p < 0.01). Bland–Altman plots showed a proportional bias for LCD1 measures. LCD1 measurements showed reasonable repeatability: ICC was 0.83 and 0.65 at 1 and 3 m, respectively. In Experiment 2, CS measured with LCD2 resulted significantly lower than Pelli–Robson both at 1 and at 3 m of about 0.10 log 1/C in both eyes (p < 0.01). Bland–Altman plots did not show any proportional bias for LCD2 measures. LCD2 measurements showed sufficient repeatability: ICC resulted 0.51 and 0.65 at 1 and 3 m, respectively. Conclusions: Computer-generated versions of Pelli–Robson test, displayed on LCD systems, do not provide accurate results compared to classic Pelli–Robson printed version. Clinicians should consider that Pelli–Robson computer-generated versions could be non-interchangeable to the printed version

    ICare Pro: Age dependent effect of central corneal thickness on intraocular pressure in glaucoma and ocular hypertension patients.

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    Purpose: Measurement of the exact intraocular pressure (IOP) is essential in glaucoma diagnosis and follow-up, thus all therapeutic options affect IOP in order to win sighted lifetime. As it is known that corneal properties of glaucoma patients differ from normal subjects, the present study aimed to investigate the influence of CCT on rebound tonometry (ICT, ICare Pro) in glaucoma and ocular hypertension patients in dependency of age additionally considering different times of day. Methods: Three hundred sixty-two eyes of 190 subjects were included: 339 open-angle glaucoma and 23 ocular hypertension. IOP was measured at 5 different times of day (6 a.m., 12 a.m., 4 p.m., 9 p.m., and 0 p.m.) by Goldmann applanation tonometry (GAT) and Icare Pro rebound tonometry in a sitting position. Central corneal thickness was measured by central ultrasonic pachymetry (Pachymeter SP-100). Δ ICT was calculated as the difference of GAT, corrected according to age and CCT, and ICT, respectively at each time point. Results: All different GAT time points data correlated significantly (p &lt;&nbsp;.05) with ICT time points. An age effect was observed on overall ICT (p =&nbsp;.02). A decrease of ICT was observed with increasing age. The within differences among ICT repeated measurements were significant as well. Additionally, repeated means of Δ ICT correlated significantly with age and CCT. Intercepts and coefficients were offered for each time point, respectively. GLM model yielded a relation between MD (dependent variable) and age together with CCT (age: p &lt;&nbsp;.0001) and (CCT: p =&nbsp;.043). Conclusions: IOP measurements with ICare Pro were shown to be dependent on age, CCT and time of day in glaucoma and ocular hypertension patients. Thus, aging, corneal biomechanical properties and circadian rhythms should be taken into consideration when adjusting IOP
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