bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amfenac together with simvastatin reduces IL‐8 and MCP‐1 and increases VEGF release from ARPE‐19 cells upon inflammatory conditions
Authors: Bhattarai Niina , Hytti Maria , Kolari Onni , Nisula Hilkka , Loukovaara Sirpa , Kauppinen Anu 
Published: December 2022

AbstractPurpose: Rhegmatogenous retinal detachment (RRD) is a sight‐threatening condition with the separation of the neurosensory retina from the retinal pigment epithelium (RPE). Clinical data have associated statin medication with lower risk of re‐vitrectomy in patients operated for RRD. We have previously shown statins to have anti‐inflammatory properties in lipopolysaccharide (LPS)‐treated RPE cells. The purpose of the present study was to examine whether the nonsteroidal anti‐inflammatory drug (NSAID) amfenac could complement the anti‐inflammatory effect of simvastatin in human RPE cells under pathophysiological conditions induced by IL‐1a. In addition to inflammatory markers, we studied the effects of amfenac and simvastatin on growth factors regulating blood vessel formation.Methods: ARPE‐19 cells were pre‐treated with 0.1 μM amfenac and 5 μM simvastatin for 24 h after which 10 pg/ml of IL‐1α was added for 24 h. Enzyme‐linked immunosorbent assay (ELISA) was used to measure secretion of cytokines (IL‐8, MCP‐1), vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF). Cytotoxicity was measured using the lactate dehydrogenase (LDH) assay.Results: Amfenac and simvastatin were well tolerated upon inflammatory conditions. Both medicines alone and together reduced IL‐1a‐activated IL‐8 release. Simvastatin significantly reduced also the release of MCP‐1. The effect of amfenac alone was not significant but together with simvastatin, significant reduction in MCP‐1 levels was still reached. IL‐1a with the DMSO solvent increased release of PEDF and VEGF compared to DMSO group. Exposure of IL‐1α‐treated cells to amfenac and simvastatin together increased VEGF levels with no changes in the PEDF.Conclusions: Amfenac and simvastatin showed potential to reduce inflammation in the retina upon retinal detachment. Increased VEGF levels may have neuroprotective effects by improving connections between RPE cells and photoreceptors.
Accelerated maturation of ARPE‐19 cells for the translational assessment of gene therapy
Authors: Locri Filippo , Bernd Jonathan , Plastino Flavia , Kvanta Anders , Andre Helder 
Published: December 2022

AbstractPurpose: Retinal pigment epithelium (RPE) modulates the exchange of metabolite products to and from the retina, and are paramount to maintain retinal function. The human RPE cell‐line ARPE‐19 is commercially available and widely used as an alternative to primary RPE. However, these cells undergo epithelial‐mesenchymal transition (EMT) losing many features of primary RPE such as polarity, pigmentation, and expression of RPE signature markers. We aimed to determine whether a combination of RPE‐specific laminin (LN) coating and media supplementation with nicotinamide (NAM) could improve ARPE‐19 expression of genes and proteins, along with morphological phenotype resembling mature RPE to improve assessment of RPE‐specific gene therapy strategies.Methods: ARPE‐19 cells were propagated on tissue culture plastic with or without NAM supplementation and/or coated with human recombinant LN‐521. Cell morphology was evaluated by phase microscopy. RPE maturation was performed by immunocytochemistry and gene expression by qPCR. Viral transduction experiments with adeno associated virus (AAV)1 or AAV2, VMD2‐driven GFP, were assessed at 2‐ and 4‐weeks post‐plating in the different culturing condition with low multiplicity of infection.Results: The combination of LN‐521 coating with NAM supplementation promoted cytoskeletal and tight junction proteins reorganization, and expression of differentiation markers such as VMD2, RPE65 and PDGFRB. In addition, the combination reduced the expression of the EMT markers, TNFα and TGF‐β1; and NCAM1, an immature phenotype RPE marker. Both AAV1‐ and AAV2‐VMD2‐GFP expression was detected from 2‐weeks and improved at 4‐weeks post‐plating.Conclusions: Our study demonstrates that the combination of NAM with LN‐521 accelerated the kinetics of expression of mature RPE signature genes, reduced expression of EMT genes, accompanied with improved epithelial cell morphology and cytoskeletal organization, bringing the dedifferentiated ARPE‐19 closer to their in vivo phenotype. Moreover, viral‐mediated RPE‐specific gene expression demonstrates the amenability of the combinatorial cultures for translational assessment of RPE gene therapies.
Vascular parameters after vitrectomy for rhegmatogenous retinal detachment, an optical coherence tomography angiography study
Authors: Bontzos George , Smoustopoulos George , Gkizis Ilias , Kontou Evgenia , Garnavou‐Xirou Christina , Xirou Stamatia‐Tina 
Published: December 2022

AbstractPurpose: To analyse vascular changes such as the postoperative foveal avascular zone (FAZ) area, the superficial vessel density (sVD) and deep vessel density (dVD) and their correlation with functional (best‐corrected visual acuity, metamorphopsia) and anatomical outcomes (foveal macular thickness, FMT) after surgery for rhegmatogenous retinal detachment (RRD) repair.Methods: Patients with RRD eyes, successfully treated with a single pars plana vitrectomy (PPV) with gas or silicone oil tamponade and a minimum 6 months follow‐up, were re‐examined. For patients where silicone oil was applied, measures were taken after its removal. Foveal avascular zone (FAZ) area, sVD, dVD and FAZ area were evaluated by using optical coherence tomography angiography (OCTA) and compared to fellow eye. Moreover, anatomical association was tested between areas of reported metamorphopsias and vascular changes in the corresponding area.Results: Twenty‐one patients with macula‐on and 24 with macula‐off RRD were included in the study. In both groups, no significant difference in macular thickness and FAZ area was found compared to fellow eyes. In macula‐on RRD eyes, a lower total dVD (p < 0.05) was detected; FAZ area was not related to FMT, and the postoperative BCVA was correlated with total DVD (p < 0.05) or FAZ area. In macula‐off RRD eyes, sDV (p = 0.012), and dVD (p = 0.05 and p < 0.05, respectively) were observed when compared to fellow eyes. The prevalence of metamorphopsia in macula‐on group was 42.86% (9/21), whereas in macula ‐off this number increased to 62.5% (15/24). For both of these groups, we found significant association between sDV and presence of metamorphopsia but only in the inferior paramacular area (p = 0.01).Conclusions: Rhegmatogenous retinal detachment eyes successfully treated with PPV had lower vessel density in the superficial and deep retinal plexus compared to fellow healthy eyes; BCVA was related to vessel density but not FAZ area. Metamorphopsias were also related to lower vessel density inferiorly of the macula.
Ocular biometric dimensions according to gender. Are they different?
Authors: Vilaplana‐Mora J. M. , Hernández Irene Gil , Hernandis José‐Miguel Hervás , Alarcón‐Correcher F. , Montero Ana López , Vidal‐Oliver L. , Duch‐Samper Antonio M. 
Published: December 2022

AbstractPurpose: To analyse ocular biometric parameters in men and women in a population of cataract surgery candidates and determine whether statistically significant differences exist.Methods: A cross‐sectional study of 5034 eyes of 2671 patients was performed. Biometric parameters of the eyes were measured by Zeiss IOLMaster 700. The axial length (AL), mean anterior radio (aR), mean posterior radio (pR), central corneal thickness (CCT), anterior chamber depth (ACD) (epithelium to lens), lens thickness (LT), and White to White corneal diameter (W2W) were evaluated. These data represent normative biometric values for the Valencian population.Results: The mean age in the male group was 73 ± 9.6 years, the mean age in the female group was 73.8 ± 8.3 years. The male/female ratio was 0.84. The male–female difference, with a 95% confidence interval (CI) in AL, ACD, and LT were 0.65 mm [0.57; 0.73] (p < 0.01), 0.17 mm [0.14; 0.2] (p < 0.01), and 0.031 mm [0.005; 0.5] (p < 0.05), respectively. Differences (95% CI) in W2W and CCT were 0.18 mm [0.15; 0.20] (p < 0.01), and 4.89 μm [2.55; 7.23] (p < 0.01). Differences (95% CI) in aR and pR were 0.137 mm [0.12; 0.153] (p < 0.01) and 0.122 mm [0.106; 0.139] (p < 0.01). All biometric eye parameters (AL, aR, pR, CCT, ACD, LT, W2W) measured, were lower in females than in males, with a statistically significant difference.Conclusions: Statistically significant differences between genders were found in all the biometric parameters evaluated. In our population, women's eyes are smaller than men's in all biometric parameters that shape them. Gender must be taken into account in the biometric evaluation of the eye. These results may be relevant in intraocular lens power calculation and in the evaluation of refractive error.
Secretory autophagy is increased in 5xFAD mice
Authors: Ruuth Johanna , Tamminen Toni , Toropainen Elisa , Koskela Ali , Korhonen Paula , Tanila Heikki , Malm Tarja , Kaarniranta Kai 
Published: December 2022

AbstractPurpose: Chronic oxidative stress, disturbed proteostasis and increased protein aggregation are key hallmarks in Alzheimer's disease and age‐related macular degeneration pathology. In this study, we assessed the protein aggregation and secretory autophagy related biomarker changes in 5xFAD mice model expressing abundant levels of human beta‐amyloid (Aβ42).Methods: The eyes of 6‐ and 12‐month‐old WT (n = 5) and 5xFAD (n = 5) were examined by immunomicroscopy. The paraffin sections were immunostained with the key regulators of secretory autophagy HMGB1, Aβ42, IL‐1β, and ferritin as well as protein aggregation markers ubiquitin protein and SQSTM1/p62.Results: Immunohistochemistry analysis revealed that ubiquitin protein conjugates and Aβ42 were increased in 6 and 12 months old 5xFAD mice. SQSTM1/p62 was decreased in 12 months old 5xFAD mice. In 12‐month‐old time point, they located basolateral side of the retinal pigment epithelial (RPE) cells but also in extracellular space. Concurrently, secretory autophagy markers were elevated in the RPE and extracellular space between RPE and Bruch's membrane.Conclusions: Secretary autophagy may be a novel regulator in drusen biogenesis. 5xFAD mouse is a good model to study protein aggregation and secretory autophagy mechanism in response to degenerative retina processes.
Multimodal imaging features in chorioretinitis sclopetaria
Authors: Ferchichi Molka , Maamouri Rym , Nouri Slim , Sassi Hela , Cheour Monia 
Published: December 2022

AbstractPurpose: To describe the multimodal imaging findings in a case of chorioretinitis sclopetaria (CS).Methods: Single case report.Results: A 26‐year‐old male reported a history of ocular injury to the right eye (OD) in childhood caused by a palm tree branch after which he underwent cataract surgery. On examination, his best‐corrected visual acuity was light perception in OD. Anterior segment examination revealed the presence of an anterior chamber intraocular lens. Intraocular pressure was within the normal range. Dilated funduscopy showed an area of bare sclera in the inferonasal quadrant adjacent to a white fibroglial proliferation that extended to the nasal and temporal periphery consistent with CS. A large area of chorioretinal atrophy involving the macular region with a nasal demarcation line and scattered hyperpigmented patches was also noted. The left eye examination was unremarkable. Fundus autofluorescence showed hypoautofluorescence of the scar tissue and in the posterior pole. Swept‐source optical coherence tomography scans confirmed the rupture of the choroid underneath a full‐thickness hyperreflectivity in the inferonasal quadrant and revealed disruptions in the macular RPE and outer retinal layers.Conclusions: CS is caused by a shock wave from a high‐velocity projectile resulting in the tearing of the choroid, retinal pigment epithelium (RPE), and neurosensory retina which later induces fibrous scarring, RPE hyperplasia, and photoreceptor loss. Multimodal imaging findings of CS are consistent with these features.
Patient‐reported outcomes measurements in dry eye patients after 84 days of daily treatment with a preservative‐free combination containing sodium hyaluronate and trehalose: The TEARS study
Authors: Mateo‐Otobia Antonio , Chassany Olivier , Duracinsky Martin 
Published: December 2022

AbstractPurpose: Dry eye disease (DED) is characterized by ocular discomfort and visual disturbance that can impact quality of life. This study evaluated, after 84 days of daily use, the improvement of ocular surface disease (OSD) and various Patient‐Reported Outcomes Measurements (PROM) in patients with DED receiving a preservative‐free combination containing sodium hyaluronate and trehalose (SH‐THL, Thealoz® Duo, Laboratoires Théa).Methods: This is a multicenter, non‐interventional survey in 312 adult subjects with DED. Clinical tests and Ocular Surface Disease Index (OSDI®) were performed at baseline and Day 84. Dry Eye Questionnaire (DEQ‐5) was done at baseline, 28 days and 84 days, as well as other PROM related to satisfaction, eye drop, comfort and impact on life's activities. SH‐THL was to be instilled when needed.Results: 82.4% were women, the mean age was 57.9 ± 15.2 years. At baseline (BL), the overall OSDI was 41.7 ± 20.6 (60.3% of patients had a severe score, i.e. between 33–100) and significantly improved after 84 days to 27.3 ± 19.8 (34.5% of patients with a severe score). Similarly, the DEQ‐5 score significantly improved at 28‐day and 84‐day visits (p < 0.001 compared to BL). Patient satisfaction with treatment significantly improved at all visits (p < 0.001 compared to BL). 72.3% preferred SH‐THL to their previous treatment after 84 days. There was a statistically significant difference in the overall scores of the impact on patient's life and the eye drop questionnaires, at all visits: 80.3% agreed on “My current drops make my eyes comfortable” at Day 84; 38.6% reported No Impact on working on a computer and 68.1% reported No Impact on sleeping at Day 84.Conclusions: The OSDI mean improvement of −14.4 points over time was higher than the minimal important difference reported in literature. Eye drops containing SH‐THL improved significantly after 84 days the Patient‐Reported Outcomes Measurements on satisfaction, eye drop, comfort and impact on life's activities in Dry Eye patients in a real‐world setting.
The role and clinical significance of intraoperative optical coherence tomography for cataract surgery
Authors: Öztek Melisa , Reyna Erick Carlos , Binder Susanne , Stieger Knut , Lytvnchuk Lyubomyr 
Published: December 2022

AbstractPurpose: to evaluate the clinical significance of intraoperative spectral domain optical coherence tomography (iOCT) in cataract surgery with implantation of different types of intraocular lenses (IOL).Methods: In this retrospective observational study, the iOCT image data of 151 cataract cases with different types of implanted IOLs were analysed. For intraoperative imaging a Rescan® 700 was used and the following image criteria were traced: standard surgical steps, IOL optic position, IOL haptic position. Patient eyes were divided into: group 1: n = 101 eyes with lens‐in‐bag (LIB); group 2: n = 15 eyes with bag‐in‐the‐lens IOL (BIL); group 3: 5 eyes with iris‐claw IOL (ICL); group 4: 15 eyes with intrascleral fixated 3‐piece IOL (3‐IOL); group 5: 15 eyes with intrascleral fixated Carlevale IOL (C‐IOL). The data were post‐processed and evaluated statistically.Results: iOCT enabled an additional control of subsequent surgical steps in all studied cases: LIB: the completeness of hydrodissection and hydrodelineation, condition of hydrated paracentesis (in 11% of cases ‐ an incomplete adaptation of paracentesis); BIL: separation of anterior hyaloid and correct implantation of capsular edges into the IOL; ICL: thickness of the iris fold between IOL claws; 3‐IOL/C‐IOL: the position of optic with regard to the iris and position of the haptic in the intrascleral space.Conclusions: The application of iOCT assisted cataract surgery with different IOLs generates useful live data that potentially reduce the risks of intra‐ and postoperative complications (posterior capsule rupture, hypotony, etc.). It can confirm the correct positioning of alternative IOL types intraoperatively, which is crucial to facilitate an optimal IOL performance. The use of iOCT shall be considered during learning process in cataract surgery.
A novel tool to study bipolar cell responses in glaucoma
Authors: Ortega Alejandro Gallego , Siga Yukihiro , Villafranca‐Baughman Deborah , Quintero Heberto , Vidal‐Sanz Manuel , Di Polo Adriana 
Published: December 2022

AbstractPurpose: Retinal ganglion cell death has been well studied in glaucoma, however how the calcium (Ca2+) dynamics in living inner retinal neurons alter to ocular hypertensive stress is poorly understood. Here we characterized a novel adeno‐associated virus (AAV) mediated Ca2+ sensor to investigate light‐evoked Ca2+ responses in bipolar cells with two‐photon laser scanning microscopy (TPLSM).Methods: To visualize ON bipolar cell specific Ca2+ expression, we bioinformatically designed a serotype 2 AAV vector carrying GCaMP6f, a Ca2+indicator, under human MiniPromoter: Ple265 (PCP2, 986 bp, AAV.Ple265.GCaMP). The AAV.Ple265.GCaMP6 was administered intravitreal to adult mice (2 μl/eye). Two and 4 weeks later (n = 3 mice/group), eyes were collected, and retinal cross sections (16 μm) were prepared for immunohistochemistry using the following primary antibodies: GFP to visualize GCaMP6f, and bipolar cell‐specific markers PCP2 or PKCa. Furthermore, we monitored real time light‐evoked Ca2+ responses in bipolar cell terminals at 4 weeks after the injection and amplitude (ΔF/F0) was calculated.Results: At 2 weeks after the viral injection, GCaMP6f was clearly visualized in bipolar cells, but its expression was limited to the cell body and dendritic trees. Four weeks post‐injection, GCaMP6f expression was abundantly detected in many bipolar cell bodies, dendrites, axons, and axonal terminals. TPLSM allowed visualization of bipolar cell‐specific GCaMP6f expression in axonal terminals in vivo, and light‐evoked sustained ON‐responses were recorded in terminal microdomains (average intensity = 1.25 ΔF/F0).Conclusions: Our study reveals that the AAV.Ple265.GCaMP is a powerful tool to monitor ON bipolar cell specific light‐evoked Ca2+ responses in bipolar cells, and can be potentially used for studies aimed at understanding the response of these neurons to glaucomatous damage.
Tlr4 gene deletion accelerates retinal degeneration in rd10 and P23H/+ murine models of retinitis pigmentosa
Authors: González Mateo Pazo , Cruz Alonso Sánchez , de la Rosa Cano Enrique J. , De La Villa Pedro , Sánchez Catalina Hernández 
Published: December 2022

AbstractPurpose: The photoreceptor degeneration associated to retinitis pigmentosa (RP) is caused by a wide variety of genetic mutations, which greatly complicates the development of a universal effective treatment. As a process independent of the causative mutation, the inflammatory response resulting from neuronal death could represent a potential candidate for a general treatment for RP. In this context, we studied the role of TLR4, one of the main mediators of innate immunity, on the retinal degenerative process in two murine models of RP.Methods: rd10 and P23H/+ mice were used to evaluate the consequences of Tlr4 haploinsufficiency and complete deletion on retinal degeneration. Visual function was evaluated by electroretinographic recordings and optomotor test and retinal cytoarchitecture by immunohistology. The myeloid cell population (main mediators of the innate immune response) reactivity was studied by immunohistology and flow cytometry. Gene expression was assessed by RT‐quantitative PCR.Results: We found that Tlr4 expression was significantly increased in the retina of both RP models. To assess the effect of Tlr4 deletion in PR progression first we confirmed that abrogation of Tlr4 expression did not impair visual function in wild‐type animals. However, Tlr4 deficiency accelerated RP progression in both rd10 and P23H/+ mice. Deletion of a single Tlr4 allele reduced the retinal electroretinographic response and photoreceptor survival in both RP models. Moreover, complete abrogation of Tlr4 further exacerbates this phenotype. These results were confirmed by assessing visual acuity by optomotor test in P23H/+ mice. Microglia analysis showed higher proportion of phagocytic microglia and lower of homeostatic microglia in the photoreceptor layers upon Tlr4 total deletion.Conclusions: The TLR4 receptor exerts a neuroprotective effect on the retinal neurodegenerative process in RP, thus suggesting a potential therapeutic target for the disease.
Characterization of rotational symmetry and noise in multifocal contact lens power maps
Authors: Raso Alicia López , Alonso Jose Manuel Lopez , Alcocer Javier Ruiz , Prieto Elena Durán , Martínez Mercedes Burgos , Goodenough Neil 
Published: December 2022

AbstractPurpose: Spherical multifocal contact lenses are typically designed with a rotationally symmetrical power profile. Imperfections in the raw material, manufacturing and measurement process can break this symmetry, altering the intended lens design. The purpose of this work is to develop a method to separate the intended symmetric design profile from the asymmetries and to give the spatial distribution of the measurement noise uncertainty in diopters.Methods: NIMO TR1504 (Lambda‐X) version V.2.13.2 has been used to measure the local power map of various multifocal contact lenses. From the map, a set of radial power profiles is obtained for different angles (0°, 180°), (0°, 360°). A symmetrical lens should show a constant radial profile for different angles, while asymmetries manifest as differences in the set of radial power profiles. They are analysed using a Principal Components Method (PCA) implemented in MATLAB.Results: The method displays a map of the symmetric radial profile of the lens, another map of the deviations with spatial structure indicating the angles where the deviations are stronger (rotational asymmetries), and noise with three separated components (spatially random variations). Asymmetries of the order of 0.17D (with maximums of 0.4D), and random noise values of 0.12D were found in some lenses.Conclusions: The characterization of multifocal contact lens prescription is important in visual optics. The prescription perceived by the patient depends on the distribution of the radial power profile on the pupil. That is the reason why asymmetries and imperfections estimation is important. The method developed in this work allows to calculate a diopter equivalent number for them.