@article{TarauBerlinCurcioetal.2019, author = {Tarau, Ioana-Sandra and Berlin, Andreas and Curcio, Christine A. and Ach, Thomas}, title = {The cytoskeleton of the retinal pigment epithelium: from normal aging to age-related macular degeneration}, series = {International Journal of Molecular Science}, volume = {20}, journal = {International Journal of Molecular Science}, number = {14}, issn = {1422-0067}, doi = {10.3390/ijms20143578}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201781}, year = {2019}, abstract = {The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions — especially in AMD.}, language = {en} } @article{WabbelsFrickeSchittkowskietal.2021, author = {Wabbels, Bettina and Fricke, Julia and Schittkowski, Michael and Gr{\"a}f, Michael and Lorenz, Birgit and Bau, Viktoria and Nentwich, Martin M. and Atili, Abed and Eckstein, Anja and Sturm, Veit and Beisse, Christina and Sterker, Ina and Neppert, Birte and Mauschitz, Matthias M.}, title = {Yokoyama procedure for esotropia associated with high myopia: real-world data from a large-scale multicentre analysis}, series = {Acta Ophthalmologica}, volume = {99}, journal = {Acta Ophthalmologica}, number = {8}, doi = {10.1111/aos.14808}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239939}, pages = {e1340 -- e1347}, year = {2021}, abstract = {Purpose High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far. Methods We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models. Results We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia. Conclusion Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large-scale real-world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.}, language = {en} } @article{DickKraussHillenkampetal.2017, author = {Dick, Julia and Krauß, Patrizia and Hillenkamp, Jost and Kohlmorgen, Britta and Schoen, Christoph}, title = {Postoperative Tropheryma whipplei endophthalmitis - a case report highlighting the additive value of molecular testing}, series = {JMM Case Reports}, volume = {4}, journal = {JMM Case Reports}, doi = {10.1099/jmmcr.0.005124}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158823}, pages = {e005124}, year = {2017}, abstract = {Introduction. Tropheryma whipplei is the causative agent of Whipple's disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms. Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1-2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei. Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple's disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.}, language = {en} } @article{BenAmiTongBhuiyanetal.2016, author = {Ben Ami, Tal and Tong, Yuehong and Bhuiyan, Alauddin and Huisingh, Carrie and Ablonczy, Zsolt and Ach, Thomas and Curcio, Christine A. and Smith, R. Theodore}, title = {Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging}, series = {Translational Vision Science \& Technology}, volume = {5}, journal = {Translational Vision Science \& Technology}, number = {3}, doi = {10.1167/tvst.5.3.5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168328}, pages = {5}, year = {2016}, abstract = {Purpose: Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging. Methods: Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436-460, 480-510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue. Results: Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location. Conclusions: There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores. Translational Relevance: Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease.}, language = {en} } @article{YousefStrzalkowskaHillenkampetal.2020, author = {Yousef, Yousef Al and Strzalkowska, Alicja and Hillenkamp, Jost and Rosentreter, Andr{\´e} and Loewen, Nils A.}, title = {Comparison of a second-generation trabecular bypass (iStent inject) to ab interno trabeculectomy (Trabectome) by exact matching}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {258}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-04933-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232613}, pages = {2775-2780}, year = {2020}, abstract = {Purpose To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. Methods Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. Results A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. Conclusion T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.}, language = {en} } @article{ChenWaxmanWangetal.2020, author = {Chen, Si and Waxman, Susannah and Wang, Chao and Atta, Sarah and Loewen, Ralitsa and Loewen, Nils A.}, title = {Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {258}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-04691-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231893}, pages = {1211-1216}, year = {2020}, abstract = {Purpose To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). Wehypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT)that removes the TM. Methods Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n= 32) and without circumferential AIT (n= 32). Cultures were exposed to 0.1, 1, and 10μM netarsudil (N= 8 eyes per concentration). For each concentration,IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters wereassessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series). Results Netarsudil at 1μM reduced IOP both in eyes with TM (-0.60 ± 0.24 mmHg,p= 0.01) and in eyes without TM (-1.79 ±0.42 mmHg,p< 0.01). At this concentration, vessels of the distal outflow tract dilated by 72\%. However, at 0.1μMnetarsudilelevated IOP in eyes with TM (1.59 ± 0.36 mmHg,p< 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg,p<0.001). Vessels of the distal outflow tract constricted by 31\%. Similarly, netarsudil at a concentration of 10μM elevated IOP both in eyeswith TM (1.91 ± 0.193,p< 0.001) and in eyes without TM (3.65 ± 0.86 mmHg,p< 0.001). At this concentration, outflow tractvessels constricted by 27\%. Conclusion In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameterchanges of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal}, language = {en} } @article{VermaFuehringDakroubHanetal.2022, author = {Verma-Fuehring, R. and Dakroub, M. and Han, H. and Hillenkamp, J. and Loewen, N. A.}, title = {Trabeculopuncture as a predictive test of distal outflow resistance in canal-based surgery}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-13990-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299740}, year = {2022}, abstract = {We investigated whether trabeculopuncture (TP) could detect distal outflow resistance to predict the outcome of canal-based glaucoma surgery such as ab interno trabeculectomy (AIT). These procedures have a high utilization in open angle glaucoma, but fail in eyes with an unidentified distal outflow resistance. We assigned 81 porcine eyes to two groups: trial (n = 42) and control (n = 39). At 24 h, four YAG-laser trabeculopunctures were placed nasally, followed by a 180° AIT at the same site at 48 h. The proportion of TP responders between both AIT groups was compared. Histology and outflow canalograms were determined. Both post-TP and post-AIT IOPs were lower than baseline IOP (p = 0.015 and p < 0.01, respectively). The success rates of TP and AIT were 69\% and 85.7\%, respectively. Sensitivity and specificity values of TP as predictive test for AIT success were 77.7\% and 83.3\%, respectively. The positive and negative predictive values were 96.6\% and 38.5\%, respectively. We conclude that a 10\% reduction in IOP after TP can be used as a predictor for the success (> 20\% IOP decrease) of 180° AIT in porcine eyes.}, language = {en} } @article{LangMessmerGeerlingetal.2015, author = {Lang, Stefan J. and Messmer, Elisabeth M. and Geerling, Gerd and Mackert, Marc J. and Brunner, Tobias and Dollak, Sylvia and Kutchoukov, Borislav and B{\"o}hringer, Daniel and Reinhard, Thomas and Maier, Philip}, title = {Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus}, series = {BMC Ophthalmology}, volume = {15}, journal = {BMC Ophthalmology}, number = {78}, doi = {10.1186/s12886-015-0070-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151498}, year = {2015}, abstract = {Background: Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy. Methods: The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model. Results: A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/-standard deviation) by 0.35 +/- 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/- 0.61 dioptres/year. This difference was statistically significant (p = 0.02). Conclusions: Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not.}, language = {en} } @phdthesis{Wobbe2023, author = {Wobbe, Christina}, title = {Hochaufgel{\"o}ste Mikroskopie mittels strukturierter Beleuchtung zur altersabh{\"a}ngigen Akkumulation autofluoreszierender Granula im retinalen Pigmentepithel des Menschen}, doi = {10.25972/OPUS-32149}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321490}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Die Technik der strukturierten Beleuchtungsmikroskopie (structured illumination microscopy, SIM) ist eine etablierte ultrastrukturelle Aufnahmemethode, die der hochaufl{\"o}senden Visualisierung intrazellul{\"a}rer Strukturen dient. In der Ophthalmologie findet diese Art der Bildgebung bisher wenig Anwendung. SIM erm{\"o}glicht die histologische Darstellung retinaler Strukturen, wie der Zellen des humanen retinalen Pigmentepithels (RPE). In den Zellen des RPE reichern sich Granula an, die f{\"u}r die Autofluoreszenz-Bildgebung von Bedeutung sind. Anhand der Morphologie und autofluoreszierenden Merkmale lassen sich grunds{\"a}tzlich drei Granulatypen im RPE unterscheiden: Melanosomen (M), Melanolipofuszin (ML)- und Lipofuszin (L)-Granula. Die Anwendung der SIM erm{\"o}glicht die pr{\"a}zise Darstellung und Differenzierung dieser autofluoreszierenden Strukturen, sowie die Bestimmung ihrer Anzahl und Lokalisation. Ziel der Arbeit ist die Darstellung der im humanen RPE lokalisierten Granula mithilfe der SIM. Anhand der unterschiedlichen Autofluoreszenz (AF) der Granula k{\"o}nnen diese innerhalb des RPE-Zellk{\"o}rpers klassifiziert, sowie deren Anzahl und Dichte analysiert werden. Diese Analyse wird in Altersgruppen und Retinalokalisationen differenziert. Zudem sind direkte Vergleiche zwischen der Histologie (SIM, ex vivo) und klinischen Aufnahmen (Fundusautofluoreszenz, in vivo) kaum existent. Durch Ermittlung der Gesamt-AF pro Zelle in Korrelation zu der intrazellul{\"a}ren Granuladichte und -verteilung soll eine neue Interpretationsebene erm{\"o}glicht werden. Diese Arbeit soll helfen anhand der gewonnenen Daten die Stoffwechselmechanismen der Retina und deren Einfluss auf die Fundusautofluoreszenz (FAF) besser verstehen zu k{\"o}nnen. Sie soll insbesondere dazu beitragen bestehende und neue klinische FAF-Bildgebungsverfahren zu validieren, die Diagnostik pathologischer Prozesse der Retina zu optimieren und sowohl eine m{\"o}glichst fr{\"u}he Erkennung als auch pr{\"a}zise Prognostik zu erm{\"o}glichen. Zudem sollen die Daten eine belastbare Basis darstellen, um die mit einem hohen Zeitaufwand verbundene manuelle Zellanalyse einer geschulten k{\"u}nstlichen Intelligenz zu {\"u}berlassen. Damit k{\"o}nnte der Analyseprozess von Gewebeproben immens beschleunigt werden und in seiner Effizienz maximiert werden.}, subject = {Netzhaut}, language = {de} } @article{DakroubVermaFuehringAgorastouetal.2022, author = {Dakroub, Mohamad and Verma-Fuehring, Raoul and Agorastou, Vaia and Sch{\"o}n, Julian and Hillenkamp, Jost and Puppe, Frank and Loewen, Nils A.}, title = {Inter-eye correlation analysis of 24-h IOPs and glaucoma progression}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {260}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, number = {10}, doi = {10.1007/s00417-022-05651-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323831}, pages = {3349-3356}, year = {2022}, abstract = {Purpose To determine whether 24-h IOP monitoring can be a predictor for glaucoma progression and to analyze the inter-eye relationship of IOP, perfusion, and progression parameters. Methods We extracted data from manually drawn IOP curves with HIOP-Reader, a software suite we developed. The relationship between measured IOPs and mean ocular perfusion pressures (MOPP) to retinal nerve fiber layer (RNFL) thickness was analyzed. We determined the ROC curves for peak IOP (T\(_{max}\)), average IOP(T\(_{avg}\)), IOP variation (IOP\(_{var}\)), and historical IOP cut-off levels to detect glaucoma progression (rate of RNFL loss). Bivariate analysis was also conducted to check for various inter-eye relationships. Results Two hundred seventeen eyes were included. The average IOP was 14.8 ± 3.5 mmHg, with a 24-h variation of 5.2 ± 2.9 mmHg. A total of 52\% of eyes with RNFL progression data showed disease progression. There was no significant difference in T\(_{max}\), T\(_{avg}\), and IOP\(_{var}\) between progressors and non-progressors (all p > 0.05). Except for T\(_{avg}\) and the temporal RNFL, there was no correlation between disease progression in any quadrant and T\(_{max}\), T\(_{avg}\), and IOP\(_{var}\). Twenty-four-hour and outpatient IOP variables had poor sensitivities and specificities in detecting disease progression. The correlation of inter-eye parameters was moderate; correlation with disease progression was weak. Conclusion In line with our previous study, IOP data obtained during a single visit (outpatient or inpatient monitoring) make for a poor diagnostic tool, no matter the method deployed. Glaucoma progression and perfusion pressure in left and right eyes correlated weakly to moderately with each other. Key messages What is known: ● Our prior study showed that manually obtained 24-hour inpatient IOP measurements in right eyes are poor predictors for glaucoma progression. The inter-eye relationship of 24-hour IOP parameters and disease progression on optical coherence tomography (OCT) has not been examined. What we found: ● 24-hour IOP profiles of left eyes from the same study were a poor diagnostic tool to detect worsening glaucoma. ● Significant inter-eye correlations of various strengths were found for all tested parameters}, language = {en} } @article{WaxmanStrzalkowskaWangetal.2023, author = {Waxman, Susannah and Strzalkowska, Alicja and Wang, Chao and Loewen, Ralitsa and Dang, Yalong and Loewen, Nils A.}, title = {Tissue-engineered anterior segment eye cultures demonstrate hallmarks of conventional organ culture}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {261}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, number = {5}, doi = {10.1007/s00417-022-05915-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323845}, pages = {1359-1368}, year = {2023}, abstract = {Background Glaucoma is a blinding disease largely caused by dysregulation of outflow through the trabecular meshwork (TM), resulting in elevated intraocular pressure (IOP). We hypothesized that transplanting TM cells into a decellularized, tissue-engineered anterior segment eye culture could restore the outflow structure and function. Methods Porcine eyes were decellularized with freeze-thaw cycles and perfusion of surfactant. We seeded control scaffolds with CrFK cells transduced with lentiviral vectors to stably express eGFP and compared them to scaffolds seeded with primary TM cells as well as to normal, unaltered eyes. We tracked the repopulation behavior, performed IOP maintenance challenges, and analyzed the histology. Results Transplanted cells localized to the TM and progressively infiltrated the extracellular matrix, reaching a distribution comparable to normal, unaltered eyes. After a perfusion rate challenge to mimic a glaucomatous pressure elevation, transplanted and normal eyes reestablished a normal intraocular pressure (transplanted = 16.5 ± 0.9 mmHg, normal = 16.9 ± 0.9). However, eyes reseeded with eGFP-expressing CrFK cells could not regulate IOP, remaining high and unstable (27.0 ± 6.2 mmHg) instead. Conclusion Tissue-engineered anterior segment scaffolds can serve as readily available, scalable ocular perfusion cultures. This could reduce dependency on scarce donor globes in outflow research and may allow engineering perfusion cultures with specific geno- and phenotypes.}, language = {en} } @phdthesis{Willmann2023, author = {Willmann, Lukas}, title = {Altersabh{\"a}ngige Makuladegeneration - Regeneration des retinalen Pigmentepithels durch Anregung zur Proliferation durch den Transkriptionsfaktor E2F2}, doi = {10.25972/OPUS-29183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-291833}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Altersbedingte Makuladegeneration (AMD) ist weltweit die h{\"a}ufigste Ursache von irreversibler Erblindung des alternden Menschen. Mit der anti-VEGF-Behandlung steht f{\"u}r die deutlich seltenere feuchte AMD eine zugelassene Therapie bereit, die deutlich h{\"a}ufigere trockene AMD entzieht sich aktuell jedoch jeglicher Therapie. Ein zentraler Pathomechanismus der AMD ist der progrediente Untergang des retinalen Pigmentepithels (RPE). Die Rarifizierung und letztendlich Atrophie des RPEs f{\"u}hrt zum Untergang der funktionellen Einheit aus RPE, Photorezeptoren und Bruch'scher Membran und somit zum irreversiblen Funktionsverlust. Ein m{\"o}glicher therapeutischer Ansatz, der progredienten Atrophie des RPEs entgegenzuwirken, ist, das prinzipiell post- mitotischen RPE zur Proliferation anzuregen. Grundlage unserer in vitro Untersuchungen ist das ARPE-19 Zellmodell. Um die Proliferation anzuregen wurden die RPE-Zellen mit E2F2, einem Zellzyklus- regulierendem Transkriptionsfaktor, transfiziert. Zun{\"a}chst wurde ein nicht-proliferatives RPE-Zellmodell mit spontanem Wachstumsarrest etabliert. Innerhalb von zwei Wochen konnte die Ausbildung von Zonulae occludentes als Zeichen der Integrit{\"a}t des adh{\"a}renten Zellmonolayers beobachtet werden. Die chemische Transfektion von E2F2 unter einem CMV-Promoter f{\"u}hrte zur {\"U}berexpression von E2F2-Protein. Der proliferationssteigernde Effekt von E2F2 konnte durch die Proliferationsmarker Cyclin D1 sowie Ki67, dem Anstieg der BrdU-Aufnahme und der nach Transfektion mit E2F2 zunehmenden Gesamtzellzahl nachgewiesen werden. Der Zellzahlerh{\"o}hung standen jedoch potentiell qualitative und funktionelle Einbußen entgegen. So zeigten sich nach Behandlung mit E2F2 die Zellviabilit{\"a}t reduziert und die Apoptoserate sowie die Permeabilit{\"a}t des Epithels erh{\"o}ht. Diese Einschr{\"a}nkungen waren jedoch nur passager bis 7 Tage nach Transfektion sichtbar und reversibel. Unsere Ergebnisse weisen darauf hin, dass diese Defizite nicht durch E2F2 selbst, sondern durch das Transfektionsreagenz PEI bedingt waren. Weitere funktionelle Defizite k{\"o}nnten durch epithelial-mesenchymale Transition (EMT) verursacht werden. Hier zeigte sich durch E2F2 keine De-Differenzierung im Sinne einer typischen EMT-Marker- Expression. Die vorliegende Arbeit zeigt in einem in vitro Zellmodell die Grundlagen eines vielversprechenden Ansatzes zur Therapie der trockenen AMD: Durch {\"U}berexpression eines den Zellzyklus regulierenden Gens (hier E2F2) wurde die RPE-Regeneration angeregt. Analog zur schon zugelassenen Gentherapie des RPEs bei RPE65-assoziierten Netzhautdystrophien durch den Transfer von funktionst{\"u}chtigem RPE65-Gen mittels Adeno-assoziierten Viren k{\"o}nnte mittels E2F2, {\"u}bertragen mit einem lentiviralen Verktor, eine Stimulation des RPEs zur Proliferation m{\"o}glich sein. Entscheidend ist der m{\"o}glichst gute Struktur- und Funktionserhalt des Photorezeptor-Bruch-Membran-RPE Komplexes. Eine Therapie sollte daher in fr{\"u}hen Krankheitsstadien erfolgen, um die Progression zu fortgeschrittenen Erkrankungsstadien mit irreversiblem Funktionsverlust zu verz{\"o}gern oder zu verhindern.}, subject = {Netzhaut}, language = {de} } @article{GuggenbergerVogtSongetal.2023, author = {Guggenberger, Konstanze V. and Vogt, Marius L. and Song, Jae W. and Weng, Andreas M. and Fr{\"o}hlich, Matthias and Schmalzing, Marc and Venhoff, Nils and Hillenkamp, Jost and Pham, Mirko and Meckel, Stephan and Bley, Thorsten A.}, title = {Intraorbital findings in giant cell arteritis on black blood MRI}, series = {European Radiology}, volume = {33}, journal = {European Radiology}, number = {4}, doi = {10.1007/s00330-022-09256-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324978}, pages = {2529-2535}, year = {2023}, abstract = {Objective Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls. Methods In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms. Results Eighteen of 56 GCA patients (32\%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths (N = 13, 72\%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms (p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures. Conclusions BB-MRI revealed inflammatory findings in the orbits in up to 32\% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms. Key Points • Up to 32\% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI. • Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI. • Features of inflammation of intraorbital structures are independent of clinically reported symptoms.}, language = {en} } @phdthesis{Radun2024, author = {Radun, Victoria}, title = {Quantitative Fundusautofluoreszenz bei systemischer (Hydroxy-)Chloroquin Therapie: ein Jahr follow-up.}, doi = {10.25972/OPUS-34868}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-348688}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {CQ und HCQ werden h{\"a}ufig zur Behandlung von Erkrankungen aus dem rheumatischen Formenkreis wie z.B. SLE oder RA eingesetzt. Die lange Anwendung birgt das Risiko der Entwicklung einer CQ/HCQ-assoziierten Makulopathie. Diese ist charakterisiert durch den irreversiblen Verlust von Photorezeptoren und RPE und im Verlauf progredienten Visusverlust. Die QAF-Bildgebung ist eine nicht-invasive, innovative Methode zur Diagnostik krankhafter Netzhautver{\"a}nderungen. Durch entsprechende technische Modifikationen eines cSLO sind inzwischen quantitative Aussagen bei Verlaufskontrollen der FAF derselben Patienten und Patientinnen sowie interpersonelle Vergleiche m{\"o}glich. In der vorliegenden Studie wurden 32 CQ/HCQ Patienten und Patientinnen {\"u}ber den Zeitraum von einem Jahr mittels multimodaler Bildgebung (IR-, FAF bei 488 nm und 787 nm, QAF bei 488 nm, rotfreie Aufnahmen sowie SD-OCT Bilder) auf BEM-typische Ver{\"a}nderungen am Augenhintergrund gescreent bzw. Verlaufskontrollen bei bekannter BEM durchgef{\"u}hrt. Die QAF Entwicklung innerhalb eines Jahres wurde quantitativ und r{\"a}umlich analysiert. Hierbei zeigte sich eine den erwarteten Alterseffekt {\"u}bersteigende Erh{\"o}hung der QAF. Dies k{\"o}nnte durch eine erh{\"o}hte Lipofuzingenese oder metabolische Aktivit{\"a}t der Netzhaut erkl{\"a}rt werden. Die vorgestellten Methoden k{\"o}nnten zuk{\"u}nftig eine n{\"u}tzliche Erweiterung zu den bereits bestehenden Diagnostik-Tools f{\"u}r Screening auf BEM sein. Bei CQ/HCQ Patienten und Patientinnen zeigt sich eine grunds{\"a}tzlich erh{\"o}hte QAF gegen{\"u}ber der Kontrollgruppe ohne das Medikament. Im Ein-Jahres-Verlauf gab es einige Patienten und Patientinnen, die einen {\"u}berdurchschnittlich starken Anstieg der QAF zeigen. Es bleibt zu kl{\"a}ren, ob diese Ausreißer Hinweise auf die sp{\"a}tere Entwicklung einer BEM liefern. So k{\"o}nnte die QAF im klinischen Alltag Anwendung finden und vor allem bei Verlaufskontrollen zus{\"a}tzliche Informationen bieten.}, subject = {Chloroquin}, language = {de} } @article{BreunFlockFeldheimetal.2023, author = {Breun, Maria and Flock, Katharina and Feldheim, Jonas and Nattmann, Anja and Monoranu, Camelia M. and Herrmann, Pia and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten and Stein, Ulrike}, title = {Metastasis associated in colorectal cancer 1 (MACC1) mRNA expression is enhanced in sporadic vestibular schwannoma and correlates to deafness}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {16}, issn = {2072-6694}, doi = {10.3390/cancers15164089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362543}, year = {2023}, abstract = {Vestibular schwannoma (VS) are benign cranial nerve sheath tumors of the vestibulocochlear nerve. Their incidence is mostly sporadic, but they can also be associated with NF2-related schwannomatosis (NF2), a hereditary tumor syndrome. Metastasis associated in colon cancer 1 (MACC1) is known to contribute to angiogenesis, cell growth, invasiveness, cell motility and metastasis of solid malignant cancers. In addition, MACC1 may be associated with nonsyndromic hearing impairment. Therefore, we evaluated whether MACC1 may be involved in the pathogenesis of VS. Sporadic VS, recurrent sporadic VS, NF2-associated VS, recurrent NF2-associated VS and healthy vestibular nerves were analyzed for MACC1 mRNA and protein expression by quantitative polymerase chain reaction and immunohistochemistry. MACC1 expression levels were correlated with the patients' clinical course and symptoms. MACC1 mRNA expression was significantly higher in sporadic VS compared to NF2-associated VS (p \< 0.001). The latter expressed similar MACC1 concentrations as healthy vestibular nerves. Recurrent tumors resembled the MACC1 expression of the primary tumors. MACC1 mRNA expression was significantly correlated with deafness in sporadic VS patients (p = 0.034). Therefore, MACC1 might be a new molecular marker involved in VS pathogenesis.}, language = {en} } @article{DopplerMeyerDovernetal.2019, author = {Doppler, Christopher E. J. and Meyer, Linda and Dovern, Anna and St{\"u}hmer-Beckh, Jaro and Weiss, Peter H. and Fink, Gereon R.}, title = {Differential impact of social and monetary reward on procedural learning and consolidation in aging and its structural correlates}, series = {Frontiers in Aging Neuroscience}, volume = {11}, journal = {Frontiers in Aging Neuroscience}, doi = {10.3389/fnagi.2019.00188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222394}, year = {2019}, abstract = {In young (n = 36, mean +/- SD: 24.8 +/- 4.5 years) and older (n = 34, mean +/- SD: 65.1 +/- 6.5 years) healthy participants, we employed a modified version of the Serial Reaction Time task to measure procedural learning (PL) and consolidation while providing monetary and social reward. Using voxel-based morphometry (VBM), we additionally determined the structural correlates of reward-related motor performance (RMP) and PL. Monetary reward had a beneficial effect on PL in the older subjects only. In contrast, social reward significantly enhanced PL in the older and consolidation in the young participants. VBM analyses revealed that motor performance related to monetary reward was associated with larger grey matter volume (GMV) of the left striatum in the young, and motor performance related to social reward with larger GMV of the medial orbitofrontal cortex in the older group. The differential effects of social reward in young (improved consolidation) and both social and monetary rewards in older (enhanced PL) healthy subjects point to the potential of rewards for interventions targeting aging-associated motor decline or stroke-induced motor deficits.}, language = {en} }