bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ca2+/ Nucleotide Nanocomplex formulation enhances the pump function of corneal endothelial cells by increasing the activity of Na+/K+ Dependent ATPase
Authors: Kang KuiDong 
Published: January 2021

AbstractPurposeNa, K‐ATPase exist in the membrane of the corneal endothelial cell and control the corneal hydration through the pump function. It also plays an important role in preserving the transparency of the cornea. In this study, we investigated the effect of Ca2+/ Nucleotide (NT) nanocomplex (NC) on Na, K‐ATPase and the pump function of the corneal endothelial cells.MethodsBovine corneal endothelial cells were used, and the cells were treated with Ca2+/ Nucleotide (NT) nanocomplex (NC) formulation after various insults. Na, K‐ATPase activity was measured by the spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate. The Na, K‐ATPase activity was calculated as the difference in ATPase activity between cells exposed to ouabain and those not exposed. Ussing chamber was used to measure the pump function of endothelial cells. Western blot analysis and immunocytochemistry were performed to measure the expression of Na, K‐ATPase α1 subunit.ResultsThe Ca2+ NT NCs were prepared at a [Ca2+]:[NT]:[bPEI 1.8 kDa] ratio of 0.25 mM:0.5 mM:1.0 mM and these preparations significantly and gradually increased the activity of Na, K‐ATPase in cultured bovine corneal endothelial cells. And these effects were effectively blocked by the PKC inhibitor (protein kinase C). In addition, Ca2+ NT NCs (0.25 mM and 0.5 mM) increased the viability of cells exposed to a low temperature (4°C) for 4 or 8 hours in a serum containing medium (p < 0.05). Western blot analysis indicated that Ca2+ NT NCs formulation significantly decreased the ratio of inactive Na, K‐Atpase α1 subunit (after 12 hours of incubation with 0.5 mM of Ca2+ NT NCs formation). Immunocytochemistry reveals that Ca2+ NT NCs formulation increased the cell surface expression of the Na,K‐ATPase α1 subunit.ConclusionsThis study demonstrates that the Ca2+ NT NC formulation increases the activity of Na, K‐ATPase in the corneal endothelial cells to enhance the pump function. Our results imply a potential therapeutic strategy that the pumping function of the corneal endothelial cells can be improved by the administration of Ca2+ NT NC formulation, which may help to maintain and improve transparency of the cornea.
Influence of the autonomic nervous system balance on pupillary response during far‐to‐near accommodation in healthy children
Authors: Bushuyeva Nataliia , Slobodianyk Svitlana , Dukhayer Shakir 
Published: January 2021

PurposeTo study the pupillary response during far‐to‐near accommodation in healthy children depending on their type of autonomic nervous system balance and the age.MethodsA total of 269 healthy children (538 eyes) aged 6–18 y.o. were examined. They were divided into three groups according to the types of autonomic nervous system balance (sympathotony, parasympathotony, normotony) using Kerdo's index: V.I. = 100 × (1–DAP/Pulse), where DAP – diastolic blood pressure (mmHg), Pulse – heart rate (beats per min). The pupil area during the far‐to‐near accommodation was measured by video‐oculography. The maximal pupil area (Smax, mm2) was measured when the eyes fixed the object at distance 100 cm, the minimal pupil area (Smin, mm2) – when the eyes fixed the object at distance 10 cm. The amplitude of pupil area change (A = Smax–Smin, mm2) was calculated. Then the amplitude of pupil area change for 1 dioptre of accommodation during far‐to‐near response was calculated as A/9 (mm2/dioptre).ResultsThe value Smax was the biggest in children with sympathotony (95% confidence 51.0–60.8 mm2), smaller in children with normotony – (20.0–44.0 mm2) and the smallest in children with parasympathotony – (19.1–32.4 mm2). In children with sympathotony, the average values of A/9 were: 4.04 ± 1.08 in children 6–9 y.o., 2.93 ± 0.17 – in children 10–14 y.o. and 3.74 ± 0.13 mm2/dioptre in teenager 15–18 y.o. The values of A/9 in children with parasympathotony were much smaller, that is 1.31 ± 0.76, 1.53 ± 0.67 and 2.24 ± 1.33 mm2/diopter, respectively. In children with normotony, the values of A/9 were the middle ones: 1.42 ± 0.65, 2.48 ± 0.89 and 3.43 ± 1.09 mm2/dioptre, respectively.ConclusionsThe difference in the amplitude of pupil area change during the far‐to‐near accommodation in healthy children aged 6 to 18 years is influenced by the type of autonomic nervous system balance. The biggest values were in children with sympathotony and the smallest in children with parasympathotony.
Use of the corneal bioreactor to assess deswelling efficacy of hyperosmotic eye drops
Authors: Peyret Benjamin , Crouzet Emmanuel , Poinard Sylvain , Garcin Thibaud , Marc Dumollard Jean , Thuret Gilles , Gain Philippe 
Published: January 2021

AbstractPurposeThe preclinical testing of the efficacy and safety of hyperosmotic anti‐edematous eye drops is complicated by the lack of a simple in vivo and ex vivo animal model. Our patented corneal bioreactor (BR) allows prolonged preservation of the human cornea by restoring physiological intraocular pressure and renewing the culture medium. Under certain experimental conditions, the corneas preserved in BR are nevertheless thicker than normal (684 ± 52 um, A J Transplantation 2019).AimTo use this characteristic of corneas stored in the BR to test the efficacy of new hyperosmotic eye drops prototypes.MethodsHuman corneas (n = 4) discarded by our eye banks were used whatever their endothelial status. They were first stored for 2 weeks into the BR filled with CorneaMax (Eurobio, France), with 21 mmHg in the endothelial chamber to allow regeneration of a normal epithelium as previously shown. Using a specific BR lid allowing sterile instillation in front of corneal center, each cornea was treated topically with 3 drops, every 2 hr, repeated 3 times. The epithelial chamber was emptied just before instillation and filled again with CorneaMax 2 min after instillation. Three corneas were treated with a commercial eyedrop containing 5% NaCl and 0.15% sodium hyaluronate and one cornea with Balanced Salt Solution (BSS) as a control. Central corneal volume (on an 8mm disc, CCV8 in mm3) was measured with OCT (Casia, Tomey) immediately before and after each instillation. The decrease in CCV was calculated for each instillation and before the first and the third instillation.ResultsFor corneas treated with NACl 5%, CCV decreased by (mean ± SD) 1.0 ± 0.4, 0.7 ± 0.1 and 0.6 ± 0.2 mm3, respectively, for the first, the second and the third instillation, and globally by 2.4 ± 1.1 mm3. The cornea treated with BSS remained unchanged.ConclusionsThe BR is an efficient tool to quantify the efficacy of hyperosmotic eye drops designed to deswell human cornea.
Retinal microglial changes at early aging in an experimental glaucoma model
Authors: Fernández‐Albarral José A. , López‐Cuenca Inés , Salobrar‐Garcia Elena , Pilar Rojas Lozano María , Ramírez Ana I. , De Hoz Rosa , Aviles‐Trigueros Marcelino , Vidal‐Sanz Manuel , Ramirez Jose Manuel , José Salazar Corral Juan 
Published: January 2021

PurposeTo analyze microglial cells activation features, and P2RY12, MHC‐II and CD68 expression in 15‐month‐old mice compared to young adult mice, after unilateral laser‐induced ocular hypertension (OHT)MethodsAlbino Swiss mice divided in four groups; young naïve (n = 6), aged naïve (n = 6), young OHT (YG) (n = 6) and aged OHT (AG) (n = 6), were analyzed. In OHT groups, both OHT eyes and contralateral eyes were studied. Retinal whole‐mounts were processed with: 1) anti Iba‐1 to quantify: i) Iba‐1 + cells number (Ibacn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); ii) area of retina occupied by Iba‐1 + cells (Iba‐1 RA) in the nerve fiber layer‐ ganglion cell layer (NFL‐GCL) iii) cell body area of Iba‐1+ cells (CbIbac) in OPL, IPL and NFL‐GCL; iv) arbor area of Iba‐1+ cells (AAIbac) in OPL and IPL; and vi) vertical processes number of Iba‐1+ cells (VPIbac) between OS and OPL. 2) anti‐P2RY12, (resident microglia), anti‐CD68 (phagocytic activity) and anti‐MHC‐II (microglial activation marker)ResultsBoth OHT eyes and contralateral eyes of YG and AG showed significant: increase of Ibacn, Iba‐1 RA, CbIbac and VPIbac and decrease of AAIbac, more pronounced in OHT eyes, compared to their respective naïve groups. Comparing YG and AG showed: i) AG versus YG in OHT eyes, significant decrease of Iba‐1 RA and VPIbac; ii) AG versus YG in contralateral eyes, a significant increase of Ibacn (OS) and a significant decrease of CbIbac and AAIbac (IPL). Analyzing the P2RY12, CD68 and MHC‐II expression we observed: i) in YG all Iba‐1+ cells were P2RY12+, except perivascular and dendritic cells, but in AG most cells were Iba‐1+/P2RY12‐; ii) in AG and YG numerous amoeboid‐like CD68+ cells were found but in AG ramified appearance CD68+ cells were also observed, and iii) While in YG practically all Iba‐1+ cells were MHC‐II+, in AG some Iba‐1+ cells showed MHC‐II+ expressionConclusionsThe morphological and molecular differences found in microglial cells of AG compared to YG show the possible aging implication in glaucoma.
Photopic negative response during and after ocular direct current stimulation
Authors: Blum Maren‐Christina , Solf Benjamin , Klee Sascha 
Published: January 2021

AbstractPurposeOcular current stimulation (CS) exhibits potential for the treatment of neurodegenerative ocular diseases. Until today, the underlying mechanism of the CS is unknown. For the pattern electroretinogram (ERG) the CS have a decreasing effect on the amplitudes but no influence on latencies. The photopic negative response (PhNR) is an amplitude in the full‐field ERG originating like the patter ERG in the GCs. The aim of the study was to investigate whether CS can also influence the PhNR.Methods14 healthy volunteers (7m, 27.7 ± 4.5 years) were stimulated with an anodal, cathodal and sham (randomized) direct CS of 800 µA for 5 min. A cut‐sized ring rubber electrode (outer/inner diameter: 7.5 cm/3 cm) placed around the eye and a square rubber electrode (25 cm2) placed at the ipsilateral temple were used for CS. Before (ERG1), during (ERG2) and after (1, 5, 10, 15 min) the CS, the PhNR was measured with a full‐field ERG (light adapted, white flash, strength: 3 cds/m2, frequency: 2 Hz, duration: < 5 ms). For ERG recording, Ag/AgCl ring‐shaped skin‐electrodes were placed at the lower eyelid (active), the ipsilateral earlobe (reference) and the forehead (ground). For analysis, the data distribution of the amplitude and latency differences to the ERG1 wasevaluated. A confidence interval analysis and the Wilcoxon test (α = 0.05, after Bonferroni correction p* ≤ 0.0167) for the difference between ERG1 and ERG2 were performed.ResultsIn the mean, the data distribution showed an increasing PhNR amplitude during the cathodal CS. The confidence interval analysis and the Wilcoxon test of the difference between ERG1 and ERG2 were significant for the cathodal CS (anodal: [−1.94 µV/2.08 µV], p = 0.826; cathodal: [0.98 µV/3.04 µV]*, p = 0.002*; sham: [−1.08 µV/0.28 µV], p = 0.272). No current effect could be found for all latencies and all after‐stimulation measurements.ConclusionsWe found a significant increase in the PhNR during a cathodal CS which suggest a modulation of GC activity.
Relationship between peripapillary perfusion density, peripapillary flow index and traditional glaucoma measurements in open‐angle glaucoma and ocular hypertension: an optical coherence tomography angiography study
Authors: Schilt‐Catafal Maria del Mar , Pérez‐Torregrosa Vicente T. , Duch‐Samper Antonio M. 
Published: January 2021

PurposeThis study aims to detect peripapillary vascular changes in patients with glaucoma and ocular hypertension compared to healthy eyes, and to correlate these vascular parameters with structural and functional parameters.Methods46 open‐angle glaucoma eyes (GE), 35 ocular hypertension eyes (OHE) and 47 age‐matched control eyes (CE) were analyzed. Visual field test was performed with the Humphrey Field Analyzer 3. Optic disc region was imaged using a 4.5 × 4.5 mm scan by a HD‐OCT Cirrus. Peripapillary perfusion density (PPD) and peripapillary flow index (PFI) were quantified by the owner’s algorithm. The statistical analysis was performed using the Kruskal‐Wallis Test with Bonferroni Post Hoc analysis and Spearman rank correlation.ResultsGE showed an attenuated PPD globally and in each sector compared to OHE and CE (−10.62%), being the superior and inferior sectors the most affected ones. PFI in GE was also lower than those in OHE and CE (−14.43%). PPD and PFI were also lower in OHE than those in CE (p < 0.001 for all pairwise comparisons). Univariate regression analysis showed that PFI was correlated with retinal nerve fiber layer (RNFL) (r = +0.607) and visual field mean deviation (VFMD) (r = +0.586). PPD had a higher correlation with RNFL (r = +0.686) and VFMD (r = +0.609). Superior and inferior sectors were the most correlated (p < 0.001 for all).ConclusionsVascular changes that occur in GE can be visualized as reduced PPD and, specially, as PFI. This finding was not previously described, and suggests that the structural damage may be caused to a greater extent by a decreased PFI more than by an attenuation of PPD. Furthermore, OHE also exhibited vascular abnormalities compared with CE. This indicates that vascular changes may occur before changes in retinal thickness at the early stages of glaucoma. All of these measures resulted to be positively correlated with traditional glaucoma parameters. So, quantitative OCTA may have value in the future to evaluate or follow up glaucoma and ocular hypertension patients.
Comparison of central corneal thickness measured by noncontact tonometry and ultrasound pachymetry
Authors: Park Hyeyeon , Young Shin Hye 
Published: January 2021

PurposeTo compare and analyze central corneal thickness (CCT) as measured by ultrasound pachymetry(USP) with noncontract tonometry(NCT) TX‐20P, which involves the function to measure central corneal thickness.MethodsThe central corneal thickness was measured in 45 eyes of 26 glaucoma patients and in 84 eyes of 43 healthy patients by two optometrist. First, noncontact tonometry TX‐20P was used to measure the CCT, followed by measurements taken using ultrasound pachymetry later. The results were compared and the correlations between two devices were analyzed. To determine whether the measurements vary depending on use of anti‐glaucoma eyedrops, all subjects were classified into two groups. Then, the difference of the CCT measured by the two devices was analyzed.ResultsThe average measurements of central corneal thickness using ultrasound pachymetry and noncontact tonometry TX‐20P were 529.07 ± 40.40 μm and 526.26 ± 35.30 μm, respectively. The central corneal thickness by ultrasound pachymetry was thicker than by noncontact tonometry TX‐20P. There was statistically significant differences between the measurements (p < 0.001) and the two exams showed high degree of linear correlation(r = 0.919, p < 0.001). The difference of central corneal thickness between two devices was 2.80 ± 19.00 μm in group 1 and 2.81 ± 14.29 μm in group 2. The difference between two groups was not statistically significant (p = 0.997).ConclusionsThis study showed that the results using ultrasound pachymetry and noncontact tonometry TX‐20P had significant positively correlation with each other regardless of using anti‐glaucoma eyedrops.
The effect of the stimulus eccentricity on the main component of the steady‐state visual evoked potential
Authors: Solf Benjamin , Blum Maren‐Christina , Klee Sascha 
Published: January 2021

PurposeFor electrophysiological functional diagnostics, the main component of steady‐state visual evoked potentials (SSVEP) at stimulation frequency (SF) is mainly used. However, some studies reported the main component at the second harmonic of the SF. A possible cause are signal components of the single responses that differ from the SF when the responses overlap during steady‐state stimulations, but the origin is not fully understood. The aim of our study was to investigate the effect of the stimulus eccentricity on the occurrence of the main component of SSVEP.MethodsWe studied 14 healthy subjects (5 m, 28 ± 5.0 years) using a circular layout (r1 = 0–1.6°, r2 = 1.6–3.5°, r3 = 3.5–6.4°, r4 = 6.4–10.9°, r5 = 10.9–18°). The dimensions of the stimuli were scaled according to the cortical magnification. The stimuli (luminance: 350 cd/m2, contrast: 99%) were presented in a random order at 7.5Hz for 75 cycles for each eccentricity. This procedure was repeated 10 times in total (750 cycles per eccentricity). A background luminance of 30 cd/m2 was added to supress foveal stray light effects. The electrodes were placed at Oz (active), FCz (reference) and FPz (ground). The recorded SSVEP were transformed using Fourier analysis. The medians (M) of the normalized amplitude ratios for amplitudes at first and second harmonic were calculated. Friedman's test (α = 0.05) and the probability of the occurrence of the main component at the second harmonic (P(MCSH)) were used for statistical analysis.ResultsThe normalized amplitude ratios showed a significant difference for the 5 stimulus eccentricities (Mr1 = 0.45, Mr2 = 0.41, Mr3 = 0.72, Mr4 = 0.72 Mr5 = 0.67; p = 0.0002*). P(MCSH) showed an increase for stimulus eccentricities for ≥r3 (P(MCSH)r1 = 0.07, P(MCSH)r2 = 0.07, P(MCSH)r3 = 0.36, P(MCSH)r4 = 0.29, P(MCSH)r5 = 0.36).ConclusionsThe stimulus eccentricity has an influence on the main component of SSVEP. An increase in stimulus eccentricity leads to an increased occurrence of the main component at second harmonic.
Offset characteristic of transient and steady‐state flash visual evoked potentials
Authors: Solf Benjamin , Blum Maren‐Christina , Klee Sascha 
Published: January 2021

PurposeIn ISCEV flash stimulations, the brief stimuli onset time results in an overlap of the onset and offset response in the recorded visual evoked potential (VEP). However, the influence of a prolonged onset time in flash stimulation has not been studied yet. The aim of our study was to investigate the effect of the onset time on the transient and steady‐state VEP.MethodsWe studied 8 healthy subjects (3 m, 26 ± 3.6 years) using flash stimuli (d = 10°, luminance = 350 cd/m2, contrast = 99%). For transient stimulations, stimuli were presented with an onset time of 16 ms, 34 ms, 67 ms, and 200 ms at 1Hz for 180 sweeps. The amplitudes and latencies of P2 and P3 peaks were used for analysis. For steady‐state stimulations, stimuli were presented with an onset time of 16 ms, 33 ms, and 67 ms at 7.5 Hz for 5 sweeps with 30 cycles each. The amplitudes at 7.5Hz and the ratio of the amplitudes at 7.5 Hz and 15 Hz were evaluated. VEPs were recorded using electrodes at Oz (active), FCz (reference) and FPz (ground). For statistical analysis, Friedman's test and Wilcoxon Post‐Hoc tests (α = 0.05) were used.ResultsFor transient stimulations, significant differences (p = 0.000*) were found for latencies of the P3 peaks (median: 201 ms, 216 ms, 230 ms, 319 ms; p*16/67 = 0.0078, p*16/200 = 0.0078, p*33/200 = 0.0078, p*67/200 = 0.0078). The P2 peak amplitude (17.6 µV, 18.1 µV, 16.6 µV, 16.2 µV; p = 0.3476), P3 peak amplitude (5.1 µV, 3.4 µV, 5.3 µV, 8.0 µV; p = 0.0917) and P2 peak latency (103 ms, 105 ms, 106 ms, 104 ms; p = 0.2453) showed no significant differences. For steady‐state stimulations, no significant differences were found for amplitudes at stimulation frequency (2.0 µV/Hz, 1.5 µV/Hz, 1.1 µV/Hz; p = 0.197) and amplitude ratio (0.5, 0.6, 0.3; p = 0.093).ConclusionsA prolonged onset time leads to a significant increase of the P3 peak latency in transient VEP. No significant influence of the onset time was found for steady‐state VEP. Thus, the steady‐state VEP seems to be dominated by the onset response of the flash stimulation.
Outcomes and complications in eyes that underwent intraocular lens fixation in the absence of capsular support
Authors: Helayel Halah , AlMutlak Mohammed , Khandekar Rajiv , AlSwailem Samar 
Published: January 2021

PurposeTo identify factors influencing the visual and refractive outcomes and complications in eyes that underwent intraocular lens fixation in the absence of capsular support.MethodsRetrospective case series. Patients records from 2014 to December 2019 in King Khaled Eye Specialist Hospital (KKESH) were reviewed and divided into two groups: posterior chamber iris fixated IOL (sutured) (IFIOL) and scleral fixated IOL (SFIOL). Demographic data, ocular factors (location of IOL placement), systemic comorbidities, lens status at the time of surgery were collected.Axial length, IOL calculation formula, surgeon level, IOL fixation technique, intraoperative complications, and concurrent or previous vitrectomy were correlated to the outcome. Postoperative data of corrected distance visual acuity, refraction, early and late postoperative complications were also collected and correlated to the outcome.ResultsSeventy‐five eyes of 69 patients were included in this study. The median follow‐up period was 9 months (range 0–60 months). The average age of patients in this study was 50 years. 14 eyes (18.6%) underwent IFIOL while 61 eyes (81.3%) underwent SFIOL. At the end of follow‐up, the preoperative mean of best‐corrected visual acuity (BCVA) was 0.3 log of the minimum angle of resolution (logMAR), which improved to 0.22 logMAR postoperatively. BCVA improved or remained unchanged in 71 eyes (94.6%), VA decreased two lines in 4 eyes (5.3%). Regular follow‐up examinations at 3, 6, and 12 months after IOL fixation revealed no intraoperative complications, and the postoperative complication rate was (18.6%).ConclusionsDifferent techniques of IOL fixation in the absence of capsular support are safe with favorable outcomes. However, they are technically challenging and time‐consuming. The innovation of new surgical techniques continues to provide safer and effective treatment options for the eyes that lack sufficient capsular support.
HDAC and HLA Class I expression in uveal melanoma
Authors: Souri Zahra , Verdijk Rob , Luyten Gregorius , Jager Martine 
Published: January 2021

PurposeHistone deacytylases (HDACs) can be a target for therapy in oncology. We determined the expression of four families of HDACs in Uveal Melanoma (UM) to see whether expression differed between low‐ and high‐risk tumors and whether their expression is related to survival.MethodsThe expression of nine HDAC’s was determined using an Illumina HT12V4 array in 64 primary UM. Tumors were divided into BAP1‐positive or ‐negative based on immune‐histochemical nuclear staining. Survival status was determined using Kaplan‐Meier analyses, using the time period between enucleation and death (mean 83 months).ResultsHigh‐risk BAP1‐negative UM (n = 30) showed a higher expression of HDAC4 (p = 0.003), HDAC7 (p = 0.02), and HDAC8 (p ≤ 0.001), and a decreased expression of HDAC11 (p ≤ 0.001) compared to BAP1‐positive UM (n = 25). When analyzing survival, we found that a high HDAC8 (p = 0.002) and low HDAC11 (p = 0.002) expression were associated with a lower overall survival.ConclusionsAs HDAC’s are being used as targets for cancer therapy, we studied the expression of a range of them in UM and identified upregulated expression of two of these epigenetic regulators in high‐risk BAP1‐negative tumors, and a down‐regulated expression of one (HDAC11). Our findings indicate that pan‐HDAC inhibitors differentially affect different HDACs and may specifically be useful for those with BAP1‐negative tumors.