Neuroglobin and cytoglobin distribution in the anterior eye segment: a comparative immunohistochemical study.
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ABSTRACT:
SUBMITTER: Ostojic J
PROVIDER: S-EPMC2516955 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neuroglobin and cytoglobin are two recently discovered members of the vertebrate globin family. Both are intracellular proteins endowed with hexacoordinated heme-Fe atoms, in their ferrous and ferric forms, and display O2 affinities comparable with that of myoglobin. Neuroglobin, which is predominantly expressed in nerve cells, is thought to protect neurons from hypoxic-ischemic injury. It is of ancient evolutionary origin, and is homologous to nerve globins of invertebrates. Cytoglobin is expressed in many different tissues, although at varying levels. It shares common ancestry with myoglobin, and can be traced to early vertebrate evolution. The physiological roles of neuroglobin and cytoglobin are not completely understood. Although supplying cells with O2 is the likely function, it is also possible that both globins act as O2-consuming enzymes or as O2 sensors. Here, we review what is currently known about neuroglobin and cytoglobin in terms of their function, tissue distribution and relatedness to the well-known hemoglobin and myoglobin. Strikingly, the data reveal that O2 metabolism in cells is more complicated than was thought before, requiring unexpected O2-binding proteins with potentially novel functional features.
| S-EPMC1308314 | biostudies-literature
Project description:PurposeTo quantify interquadrant differences in anterior chamber angle (ACA) configuration assessed on gonioscopy, EyeCam, and anterior segment optical coherence tomography (AS-OCT) in a cohort of Chinese Americans.MethodsSubjects aged 50 years or older were recruited from the Chinese American Eye Study (CHES), a population-based epidemiologic study in Los Angeles, CA. Each subject underwent a complete ocular exam, including gonioscopy, EyeCam, and AS-OCT, under dark ambient lighting. Gonioscopy and AS-OCT imaging and EyeCam image grading were performed by trained ophthalmologists.ResultsSeven hundred nine eyes from 709 subjects were analyzed. Less anatomic variation among the quadrants was detected on gonioscopy and EyeCam compared with AS-OCT (P < 0.05). The mean gonioscopy grade, EyeCam grade, and AS-OCT measurement for each quadrant varied by up to 10.3%, 6.4%, and 46.2% of the superior quadrant value, respectively. There were significant interquadrant differences (P < 0.05) among mean AOD750 measurements when grouping by quadrant and gonioscopy or EyeCam grade. Mean AOD750 measurements were smallest for the superior quadrant by between 14.3% and 38.1% and 17.4% and 37.9% on gonioscopy and EyeCam, respectively, compared with other quadrants.ConclusionsGonioscopy and EyeCam significantly underrepresent anatomic variations of the ACA compared with AS-OCT. Gonioscopy or EyeCam grades from different quadrants do not appear to be comparable or interchangeable, which supports reconsideration of current definitions and methods used to diagnose and manage primary angle closure disease.Translational relevanceAS-OCT imaging raises concerns about current clinical definitions and methods that rely gonioscopy or EyeCam to assess the ACA.
| S-EPMC6438105 | biostudies-literature
Project description:BackgroundThe prognostic significance of debridement has long been demonstrated for trauma in tissues other than ocular. Unfortunately, the impact of wound healing in the anterior segment (AS) was not paid as much attention as in the posterior segment (PS). This study aims to evaluate whether a better prognosis can be obtained from continuous surgical treatment (CST) before fibrosis or scar formation in an open AS injury.MethodsIn this prospective comparative cohort study, 19 eyes of 19 patients with an experience of AS open globe injury (OGI) were selected from the database of the eye injury vitrectomy study (EIVS) from January 1, 2020 to July 31, 2021. Of 19 patients, 9 who received CST were assigned to group 1, and 10 patients without CST after the initial wound repair were included in group 2. Comparison between the two groups was conducted in the final best corrected visual acuity (BCVA). Significant AS complications after injury were evaluated with χ2 test. The corneal leucoma area ratio, astigmatism, and the score of AS abnormalities were analyzed using the Student's t-test.ResultsThe differences of baseline clinical factors between the two groups were not statistically significant. The final BCVA was better in group 1 than in group 2 (P=0.011). The complications directly caused by AS injury, namely adhesive corneal leucoma, uneven anterior chamber, block of light passing through the pupil, and fibrosis or scarring, were more frequent in group 2 than in group 1 (P=0.011, 0.022, 0.037, and 0.040, respectively). Secondary glaucoma (3 cases) and severe AS structure destruction (2 cases) occurred only in group 2 (P=0.037 and 0.474, respectively). The area ratio of leucoma (0.79±0.44, 0.82±0.50, respectively) and corneal astigmatism (3.69±1.90, 4.50±4.80, respectively) revealed no statistical significance between the two groups. On the other hand, the score of AS abnormalities, mean values being 93.33±11.18 for group 1 and 67.00±29.46 for group 2, was statistically different (P=0.022).ConclusionsInitiating CST before fibrosis or scar formation might improve the prognosis of open AS injury, which was preferable to natural wound healing after wound repair.
| S-EPMC10498217 | biostudies-literature
Project description:Purpose To investigate the influences of atropine on changes in anterior segment geometry, as measured by ultrasound biomicroscopy in children. Methods A prospective observational study was performed. Anterior segment parameters were obtained by UBM before and after the instillation of 1% atropine. Univariate linear regression was performed to identify the variables contributing to the changes in the trabecular meshwork-iris angle (TIA). Results The study included 21 boys and 37 girls with a mean age of 10.79?±?2.53 years. Anterior chamber parameters including the central anterior chamber depth, TIA, angle opening distance at 500??m from the scleral spur, iris thickness 750??m and 1500??m from the scleral spur, trabecular-ciliary angle (TCA), trabecular-ciliary process distance, sclera-iris angle (SIA), and sclera-ciliary process angle significantly increased after cycloplegia (P < 0.05). In contrast, the lens vault, iris cross-sectional area, and maximum ciliary muscle thickness significantly decreased after cycloplegia. Univariate analysis identified the change in TCA and the change in SIA and the TIA before mydriasis as determinants of the change in TIA. Conclusions Atropine causes statistically significant changes in various anterior segment parameters in children. The change in anterior chamber angle is associated with the change in TCA and the change in SIA and the TIA before mydriasis.
| S-EPMC7539084 | biostudies-literature
Project description:Anterior segment eye diseases account for a significant proportion of presentations to eye clinics worldwide, including diseases associated with corneal pathologies, anterior chamber abnormalities (e.g. blood or inflammation), and lens diseases. The construction of an automatic tool for segmentation of anterior segment eye lesions would greatly improve the efficiency of clinical care. With research on artificial intelligence progressing in recent years, deep learning models have shown their superiority in image classification and segmentation. The training and evaluation of deep learning models should be based on a large amount of data annotated with expertise; however, such data are relatively scarce in the domain of medicine. Herein, the authors developed a new medical image annotation system, called EyeHealer. It is a large-scale anterior eye segment dataset with both eye structures and lesions annotated at the pixel level. Comprehensive experiments were conducted to verify its performance in disease classification and eye lesion segmentation. The results showed that semantic segmentation models outperformed medical segmentation models. This paper describes the establishment of the system for automated classification and segmentation tasks. The dataset will be made publicly available to encourage future research in this area.
| S-EPMC8982547 | biostudies-literature
Project description:BackgroundCytoglobin (Cygb) and neuroglobin (Ngb) are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM) cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX), a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia.ResultsCygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel) showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo.ConclusionsOur finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human tumor tissues suggests that these globin molecules may be part of the repertoire of defense mechanisms that allow cancer cells to survive in hypoxic microenvironments.
| S-EPMC2945342 | biostudies-literature
Project description:BackgroundGlaucoma 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.MethodsPorcine 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.ResultsTransplanted 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.ConclusionTissue-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.
| S-EPMC10148776 | biostudies-literature
Project description:Topical drug delivery is one of the most challenging aspects of eye therapy. Eye drops are the most prevalent drug form, especially for widely distributed anterior segment eye diseases (cataracts, glaucoma, dry eye syndrome, inflammatory diseases, etc.), because they are convenient and easy to apply by patients. However, conventional drug formulations are usually characterized by short retention time in the tear film, insufficient contact with epithelium, fast elimination, and difficulties in overcoming ocular tissue barriers. Not more than 5% of the total drug dose administered in eye drops reaches the interior ocular tissues. To overcome the ocular drug delivery barriers and improve drug bioavailability, various conventional and novel drug delivery systems have been developed. Among these, nanosize carriers are the most attractive. The review is focused on the different drug carriers, such as synthetic and natural polymers, as well as inorganic carriers, with special attention to nanoparticles and nanomicelles. Studies in vitro and in vivo have demonstrated that new formulations could help to improve the bioavailability of the drugs, provide sustained drug release, enhance and prolong their therapeutic action. Promising results were obtained with drug-loaded nanoparticles included in in situ gel.
| S-EPMC8621153 | biostudies-literature
Project description:The subterranean mole rat Spalax is an excellent model for studying adaptation of a mammal toward chronic environmental hypoxia. Neuroglobin (Ngb) and cytoglobin (Cygb) are O(2)-binding respiratory proteins and thus candidates for being involved in molecular hypoxia adaptations of Spalax. Ngb is expressed primarily in vertebrate nerves, whereas Cygb is found in extracellular matrix-producing cells and in some neurons. The physiological functions of both proteins are not fully understood but discussed with regard to O(2) supply, the detoxification of reactive oxygen or nitrogen species, and apoptosis protection. Spalax Ngb and Cygb coding sequences are strongly conserved. However, mRNA and protein levels of Ngb in Spalax brain are 3-fold higher than in Rattus norvegicus under normoxia. Importantly, Spalax expresses Ngb in neurons and additionally in glia, whereas in hypoxia-sensitive rodents Ngb expression is limited to neurons. Hypoxia causes an approximately 2-fold down-regulation of Ngb mRNA in brain of rat and mole rat. A parallel regulatory response was found for myoglobin (Mb) in Spalax and rat muscle, suggesting similar functions of Mb and Ngb. Cygb also revealed an augmented normoxic expression in Spalax vs. rat brain, but not in heart or liver, indicating distinct tissue-specific functions. Hypoxia induced Cygb transcription in heart and liver of both mammals, with the most prominent mRNA up-regulation (12-fold) in Spalax heart. Our data suggest that tissue globins contribute to the remarkable tolerance of Spalax toward environmental hypoxia. This is consistent with the proposed cytoprotective effect of Ngb and Cygb under pathological hypoxic/ischemic conditions in mammals.
| S-EPMC3003035 | biostudies-literature
Project description:PurposeTo develop a deep neural network that detects the scleral spur in anterior segment optical coherence tomography (AS-OCT) images.MethodsParticipants in the Chinese American Eye Study, a population-based study in Los Angeles, California, underwent complete ocular examinations, including AS-OCT imaging with the Tomey CASIA SS-1000. One human expert grader provided reference labels of scleral spur locations in all images. A convolutional neural network (CNN)-based on the ResNet-18 architecture was developed to detect the scleral spur in each image. Performance of the CNN model was assessed by calculating prediction errors, defined as the difference between the Cartesian coordinates of reference and CNN-predicted scleral spur locations. Prediction errors were compared with intragrader variability in detecting scleral spur locations by the reference grader.ResultsThe CNN was developed using a training dataset of 17,704 images and tested using an independent dataset of 921 images. The mean absolute prediction errors of the CNN model were 49.27 ± 42.07 µm for X-coordinates and 47.73 ± 39.70 µm for Y-coordinates. The mean absolute intragrader variability was 52.31 ± 47.75 µm for X-coordinates and 45.88 ± 45.06 µm for Y-coordinates. Distributions of prediction errors for the CNN and intragrader variability for the reference grader were similar for X-coordinates (P = 0.609) and Y-coordinates (P = 0.378). The mean absolute prediction error of the CNN was 73.08 ± 52.06 µm and the mean absolute intragrader variability was 73.92 ± 60.72 µm.ConclusionsA deep neural network can detect the scleral spur on AS-OCT images with performance similar to that of a human expert grader.Translational relevanceDeep learning methods that automate scleral spur detection can facilitate qualitative and quantitative assessments of AS-OCT images.
| S-EPMC7395674 | biostudies-literature