Health problems caused by airborne particulate matter with a diameter less than 2.5 (PM2.5), especially in the respiratory system, have become a worldwide problem, but the influence and mechanisms of ...PM2.5 on the ocular surface have not been sufficiently elucidated. We investigated in vitro the onset and pathogenesis of corneal damage induced by PM2.5. Two types of PM2.5 samples originating from Beijing (designated #28) and the Gobi Desert (designated #30) were added to the culture medium of immortalized cultured human corneal epithelial cells (HCECs) to examine the effects on survival rates, autophagy, and proinflammatory cytokine production. Both types of PM2.5 significantly reduced the HCEC survival rate in a concentration-dependent manner by triggering autophagy. In particular, compared with #30, #28 induced much more severe damage in HCECs. Physical contact between PM2.5 and HCECs was not a primary contributor to PM2.5-induced HCEC damage. Among the 38 proinflammatory cytokines examined in this study, significant increases in the granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-6 levels and a significant reduction in the interleukin-8 level were detected in culture medium of PM2.5-exposed HCECs. Simultaneous addition of a GM-CSF inhibitor, suramin, alleviated the HCEC impairment induced by PM2.5. In conclusion, PM2.5 induces HCEC death by triggering autophagy. Some cytokines that are released from HCECs, including GM-CSF, may be involved in HCEC damage caused by PM2.5 exposure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose. We aimed to investigate squeezing force and dispensing time interval of the first and second eye drops among a variety of eyedropper bottles and to clarify associated factors within these ...parameters. Methods. A total of 87 eyedropper bottles were involved in this study. We developed a squeezing force measuring system consisting of a syringe pump, digital force gauge, and custom-made test stand to measure the squeezing force and dispensing interval. The eyedropper bottle was housed in the system vertically, and measurements were repeated five times. We investigated the differences in squeezing force and dispensing interval by categories, including those that targeted ocular disease, brand or generic eyedroppers, shapes of eyedropper bottles, and the presence of a membrane filter inside the tip of the eyedropper bottle. Results. The mean squeezing forces of the first drop and the second drops were 8.3 ± 3.0 N and 10.4 ± 3.2 N, respectively. Both squeezing forces had a wide variation of more than threefold. A mean interval between the first and second drops was 3.1 ± 1.2 sec with a maximum difference of more than sevenfold. Round shapes of eyedropper bottles and the presence of filter membranes significantly increased the squeezing force. Conclusions. The squeezing force of eyedropper bottles was very wide, which may affect proper eye drop instillation. Unification of eyedropper bottles or developing mechanical aids may be useful for proper eye drop treatment.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
In 2017, the Japanese Ophthalmological Society (JOS) created the Japan Ocular Imaging (JOI) registry, a national database of images and clinical data in the field of ophthalmology in Japan. The JOI ...registry automatically transfers the information stored in the electronic medical records of each institution to the cloud storage governed by the JOS. This process adheres to Japanese laws and regulations such as the Act on the Protection of Personal Information and the relevant laws of Japan, the Ethical Guidelines for Medical and Biological Research Involving Human Subjects, and the Medical Information System Security Management Guideline of Japan. The JOI registry works closely with academia in ophthalmology, as well as the Japan Association for Medical Informatics, the Japan Ophthalmic Instrument Association, and manufacturers of ophthalmic medical devices. The collected data will be used in studies and surveys to improve the quality of ophthalmic care. The JOI registry has been created as a common asset for the entire ophthalmology field, and welcomes participation of related institutions to utilize the infrastructure to promote multicenter joint research and development. The JOI registry network intends to cover all ophthalmological facilities, including clinics. However, the project is currently being conducted with the cooperation of 22 university hospitals, one private hospital, and two health checkup facilities. As of October 2021, six facilities are connected to the JOI registry network; it comprises a total of 486,189 fundus images, 25,224 optical coherence tomography images, and 11,565 visual field results, among others, are stored in the JOI registry. This project was initially funded by a national funding agency, the Japan Agency for Medical Research and Development (AMED) (ICT Infrastructure Establishment and Implementation of Artificial Intelligence for Clinical and Medical Research, 2017–2019). The General Incorporated Association Japan Ocular Imaging Registry was established in 2019, following which the association is managing the JOI registry under the governance of the JOS. The JOI registry is aiming to become a large-scale real-world database comparable to the Intelligent Research in Sight registry of the United States.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
4.
Astrocyte Immune Functions and Glaucoma Shinozaki, Youichi; Kashiwagi, Kenji; Koizumi, Schuichi
International journal of molecular sciences,
2023-Feb-01, 2023-02-01, 20230201, Volume:
24, Issue:
3
Journal Article
Peer reviewed
Open access
Astrocytes, a non-neuronal glial cell type in the nervous system, are essential for regulating physiological functions of the central nervous system. In various injuries and diseases of the central ...nervous system, astrocytes often change their phenotypes into neurotoxic ones that participate in pro-inflammatory responses (hereafter referred to as "immune functions"). Such astrocytic immune functions are not only limited to brain diseases but are also found in ocular neurodegenerative diseases such as glaucoma, a retinal neurodegenerative disease that is the leading cause of blindness worldwide. The eye has two astrocyte-lineage cells: astrocytes and Müller cells. They maintain the physiological environment of the retina and optic nerve, thereby controlling visual function. Dysfunction of astrocyte-lineage cells may be involved in the onset and progression of glaucoma. These cells become reactive in glaucoma patients, and animal studies have suggested that their immune responses may be linked to glaucoma-related events: tissue remodeling, neuronal death, and infiltration of peripheral immune cells. In this review, we discuss the role of the immune functions of astrocyte-lineage cells in the pathogenesis of glaucoma.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Excitotoxicity is well known in the neuronal death in the brain and is also linked to neuronal damages in the retina. Recent accumulating evidence show that microglia greatly affect excitotoxicity in ...the brain, but their roles in retina have received only limited attention. Here, we report that retinal excitotoxicity is mediated by microglia. To this end, we employed three discrete methods, that is, pharmacological inhibition of microglia by minocycline, pharmacological ablation by an antagonist for colony stimulating factor 1 receptor (PLX5622), and genetic ablation of microglia using Iba1‐tTA::DTAtetO/tetO mice. Intravitreal injection of NMDA increased the number of apoptotic retinal ganglion cells (RGCs) followed by reduction in the number of RGCs. Although microglia did not respond to NMDA directly, they became reactive earlier than RGC damages. Inhibition or ablation of microglia protected RGCs against NMDA. We found up‐regulation of proinflammatory cytokine genes including Il1b, Il6 and Tnfa, among which Tnfa was selectively blocked by minocycline. PLX5622 also suppressed Tnfa expression. Tumor necrosis factor α (TNFα) signals were restricted in microglia at very early followed by spreading into other cell types. TNFα up‐regulation in microglia and other cells were significantly attenuated by minocycline and PLX5622, suggesting a central role of microglia for TNFα induction. Both inhibition of TNFα and knockdown of TNF receptor type 1 by siRNA protected RGCs against NMDA. Taken together, our data demonstrate that a phenotypic change of microglia into a neurotoxic one is a critical event for the NMDA‐induced degeneration of RGCs, suggesting an importance of non‐cell‐autonomous mechanism in the retinal neuronal excitotoxicity.
Main Points
Microglia have a critical role for the N‐methyl‐d‐aspartate (NMDA)‐induced neuronal damages in the retina, although they do not respond to NMDA directly. For such microglia‐mediated noncell‐autonomous mechanisms, TNFα has a central role.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The aim of the study was to investigate the usefulness of processing visual field (VF) using a variational autoencoder (VAE). The training data consisted of 82,433 VFs from 16,836 eyes. Testing ...dataset 1 consisted of test-retest VFs from 104 eyes with open angle glaucoma. Testing dataset 2 was series of 10 VFs from 638 eyes with open angle glaucoma. A VAE model to reconstruct VF was developed using the training dataset. VFs in the testing dataset 1 were then reconstructed using the trained VAE and the mean total deviation (mTD) was calculated (mTD
). In testing dataset 2, the mTD value of the tenth VF was predicted using shorter series of VFs. A similar calculation was carried out using a weighted linear regression where the weights were equal to the absolute difference between mTD and mTD
. In testing dataset 1, there was a significant relationship between the difference between mTD and mTD
from the first VF and the difference between mTD in the first and second VFs. In testing dataset 2, mean squared prediction errors with the weighted mTD trend analysis were significantly smaller than those form the unweighted mTD trend analysis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
To investigate the treatment persistence of carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution (CAR/LAT) and other β-blocker/prostanoid FP receptor agonist ...fixed-combination ophthalmic solutions (BB/FP) in the treatment of glaucoma.
Study design
Retrospective observational cohort study.
Methods
A retrospective observational cohort study using JMDC Claims Database. Patients aged 20 years or older diagnosed with glaucoma between February 1, 2017, and March 31, 2020, and prescribed CAR/LAT or another BB/FP were included.
Results
A total of 16,612 patients (7423 in the CAR/LAT group and 9189 in the other BB/FP group) were included. The cumulative treatment persistence rate at the end of follow-up was 42.0% (64.9% at 1 year, 53.4% at 2 years, 45.0% at 3 years, and 42.0% at 4 years) in the CAR/LAT group and 34.7% (54.8% at 1 year, 43.6% at 2 years, 37.1% at 3 years, and 34.7% at 4 years) in the other BB/FP group. Treatment persistence was significantly longer in the CAR/LAT group compared to that in the other BB/FP group (hazard ratio 0.747, p < 0.0001). Over the treatment period, the number of patients who discontinued treatment was 3281 (44.2%) in the CAR/LAT group and 4926 (53.6%) in the other BB/FP group; the median duration of treatment was 135 days and 97 days, respectively.
Conclusion
The study results suggest that persistence rates vary depending on the BB/FP and CAR/LAT appears to be more persistent than other BB/FP.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diabetic macular edema (DME) causes severe vision loss among patients with diabetes mellitus (DM). We aimed to investigate systemic and ocular diseases associated with the development of DME in a ...Japanese population.
A total of 3.11 million Japanese subjects who were registered in the database of the Japan Medical Data Center from 2005 to 2014 were analyzed. Subjects with DM were defined as individuals who had been prescribed any therapeutic medications for DM, and associated diseases were analyzed. The periods assessed were one year before the development of DME among patients with DME and one year before the last visit to an ophthalmic clinic among patients without DME.
A total of 17,403 patients with DM satisfied the inclusion and exclusion criteria, and 420 patients developed DME. Univariate analysis revealed significant associations between 55 diseases, including 39 systemic and 16 ocular diseases, and DME development. Logistic analysis identified 21 systemic diseases and 10 ocular diseases as significant factors associated with DME development.
Various types of systemic and ocular diseases are associated with DME development. Subjects with DM who present these risk factors must be carefully monitored to prevent visual impairment.
The aim of this study was to investigate the frequency of eyedrop instillation failure and its related physical and visual function factors among glaucoma patients who used hypotensive eyedrops ...daily.
Patients with a history of self-instillation of one or more ocular hypotensive ophthalmic solutions for six or more months were enrolled. Definitions of instillation failure were eyedrop instillation other than on the eye surface; eyedrop contact with eyelashes; eyedrop bottle tip contact with the eyelashes, eye surface or ocular adnexa; or two or more drops instilled with one instillation trial. To clarify factors related to instillation failure, we used visual function tests and investigated cervical spine extension angles during instillation, pinching strength, physical ataxia (evaluated using the Scale for the Assessment and Rating of Ataxia), motor dysfunction of the upper limbs (evaluated using the Disabilities of the Arm, Shoulder and Hand questionnaire), and vision quality (evaluated using the National Eye Institute Visual Function Questionnaire 25).
Of 103 total subjects, 61.2% satisfied the definition of instillation failure. Instillation of the eyedrop other than at the cul-desac (76.2%) was the most frequent reason for failure, followed by contact of the tip of the eyedrop bottle (22.2%) and instillation of the same or more than two eyedrops in a single attempt (11.1%). Advanced age, a shallow cervical spine extension angle, weak pinching strength, poor motor dysfunction of the upper limbs, the degree of ataxia, poor best-corrected visual acuity, and visual field scores were significant risk factors for instillation failure. Vision quality may have some relation to instillation failure.
It is highly recommended that instillation failure be routinely investigated even among patients with adequate experience using eyedrops and that correct therapies are chosen in a patient-based fashion.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To develop a large-scale real clinical database of glaucoma (Japanese Archive of Multicentral Databases in Glaucoma: JAMDIG) and to investigate the effect of treatment.
The study included a total of ...1348 eyes of 805 primary open-angle glaucoma patients with 10 visual fields (VFs) measured with 24-2 or 30-2 Humphrey Field Analyzer (HFA) and intraocular pressure (IOP) records in 10 institutes in Japan. Those with 10 reliable VFs were further identified (638 eyes of 417 patients). Mean total deviation (mTD) of the 52 test points in the 24-2 HFA VF was calculated, and the relationship between mTD progression rate and seven variables (age, mTD of baseline VF, average IOP, standard deviation (SD) of IOP, previous argon/selective laser trabeculoplasties (ALT/SLT), previous trabeculectomy, and previous trabeculotomy) was analyzed.
The mTD in the initial VF was -6.9 ± 6.2 dB and the mTD progression rate was -0.26 ± 0.46 dB/year. Mean IOP during the follow-up period was 13.5 ± 2.2 mm Hg. Age and SD of IOP were related to mTD progression rate. However, in eyes with average IOP below 15 and also 13 mm Hg, only age and baseline VF mTD were related to mTD progression rate.
Age and the degree of VF damage were related to future progression. Average IOP was not related to the progression rate; however, fluctuation of IOP was associated with faster progression, although this was not the case when average IOP was below 15 mm Hg.
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