Publications by authors named "Kenji Matsushita"

116 Publications

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren's Syndrome Model Mice.

Int J Mol Sci 2021 Feb 25;22(5). Epub 2021 Feb 25.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu 474-8511, Japan.

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4 T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren's syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.
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http://dx.doi.org/10.3390/ijms22052302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956724PMC
February 2021

Efficacy and safety of 5-fluorouracil in infrared monitor guided bleb revision.

BMC Ophthalmol 2021 Feb 8;21(1):75. Epub 2021 Feb 8.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Room E7, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Purpose: Infrared monitor-guided bleb revision (IRGBR), an alternative needling system, visualizes anterior-segment tissues around the bleb not visible during needle revision after trabeculectomy. This study determined the safety and efficiency of 5-fluorouracil (5-FU) as an adjunctive anti-metabolite in IRGBR.

Methods: We retrospectively analyzed 43 consecutive eyes (40 patients; 14 eyes, primary open-angle; 29 eyes, secondary glaucoma) treated with IRGBR for failing filtering blebs. The patients were divided into two groups. The first one had IRGBR without adjunctive 5-FU subconjunctival injection, and the second one had IRGBR with 5-FU. We performed Kaplan-Meier survival analysis using log-rank tests after 2 years of follow-up and Cox proportional hazards regression model to analyze the dependence of the survival time on predictor variables. Two failure criteria were defined as the need for additional surgery for intraocular pressure (IOP) reduction and the IOP at two consecutive follow-up visits based on definition 1, IOP ≧22 mmHg and definition 2, IOP ≧17 mmHg.

Results: Thirty eyes (29 cases) underwent IRGBR with subconjunctival 5-FU injection (group A in the second term) and 13 eyes (11 cases) without 5-FU (group B in the first term). The success rates 24 months after IRGBR were 73.3 and 23.1%, respectively, in groups A and B based on the definition 1 failure and 56.7 and 7.7% based on the definition 2 failure. Complications included transient bleb leaks (group A, 3 eyes; group B, none) and choroidal detachment (group A, 1 eye; group B, none). No use of 5-FU and IOPs ≧10 mmHg 1 week after IRGBR were significant risk factors.

Conclusions: Adjunctive 5-FU in IRGBR achieved a better success rate for failing trabeculectomy blebs.
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http://dx.doi.org/10.1186/s12886-021-01843-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869480PMC
February 2021

Effect of green propolis extracts on experimental aged gingival irritation in vivo and in vitro.

J Oral Biosci 2021 03 21;63(1):58-65. Epub 2021 Jan 21.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu City, Aichi, 474-8511, Japan. Electronic address:

Objectives: Tooth bleaching has become one of the most frequently requested esthetic procedures in dental practice. A side effect of bleaching is gingival irritation. This study examined the efficacy of propolis to treat gingival irritation caused by bleaching in vivo and in vitro.

Methods: Gingival irritation was mimicked by a mild burn injury to oral mucosa in young (10 week old) and aged (18 month old) mice. Propolis ointment was immediately applied to the burn area. After 24 h, gingiva was collected to determine the efficacy of propolis by hematoxylin and eosin staining and real-time polymerase chain reaction (PCR).

Results: Topical application of propolis ointment reduced the infiltration of inflammatory cells at irritated sites and promoted the repair of the mucosal epithelium in young and aged mice. It also suppressed the expression of IL-1β and TNF-α and increased keratin 1 and 5 expression in the irritated gingiva. Propolis suppressed an increase in IL-1β and TNF-α upon stimulation with HO in young and SA-β-gal-expressing senescent human gingival fibroblasts (HGFs) cultures.

Conclusions: Propolis may be effective for mucosal repair in gingival irritation as it suppresses the expression of proinflammatory cytokines and promotes keratin expression.
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http://dx.doi.org/10.1016/j.job.2020.12.003DOI Listing
March 2021

Efficacy and Safety of Intravitreal Aflibercept Injection in Japanese Patients with Neovascular Glaucoma: Outcomes from the VENERA Study.

Adv Ther 2021 02 16;38(2):1106-1115. Epub 2020 Dec 16.

Bayer Consumer Care AG, Basel, Switzerland.

Introduction: Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma.

Methods: This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1.

Results: Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, -8.3 mmHg [95% confidence interval; CI -12.2 to -4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8-70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%).

Conclusions: IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma.

Trial Registration: Clinicaltrials.gov identifier NCT03639675.
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http://dx.doi.org/10.1007/s12325-020-01580-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889553PMC
February 2021

Intravitreal Aflibercept in Japanese Patients with Neovascular Glaucoma: The VEGA Randomized Clinical Trial.

Adv Ther 2021 02 16;38(2):1116-1129. Epub 2020 Dec 16.

Bayer Consumer Care AG, Basel, Switzerland.

Introduction: Neovascular glaucoma is characterized by neovascularization of the iris and the anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may improve intraocular pressure (IOP) and neovascularization.

Methods: The VEGA trial assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma in a 13-week, randomized, double-masked, sham-controlled, phase 3 study performed at multiple sites in Japan that enrolled patients with anterior segment neovascularization and IOP > 25 mmHg. Patients received background therapy plus IVT-AFL (2 mg) or sham injection at baseline. Patients were re-treated if presenting with IOP > 21 mmHg and incomplete regression of iris neovascularization, receiving additional sham or IVT-AFL injections at week 1 and IVT-AFL injections at weeks 5 and/or 9. Double-masking was maintained throughout. The primary endpoint was change in IOP from baseline to week 1.

Results: Fifty-four patients were randomly assigned (full analysis set); the per-protocol set comprised 52 patients. At week 1, the least squares mean change in IOP was -9.9 mmHg for IVT-AFL versus -5.0 mmHg for sham [full analysis set: difference -4.9 mmHg (95% confidence interval -10.2 to 0.3; P = 0.06); per-protocol set: -5.5 mmHg (95% CI -10.8 to -0.2; P = 0.04)]. At week 1, a greater proportion of patients administered IVT-AFL versus sham achieved IOP ≤ 21 mmHg and had improved neovascularization grades. Patients in the sham group who met re-treatment criteria and received IVT-AFL at week 1 [n = 22 (81.5%)] had an additional mean IOP decrease of 9.2 mmHg by week 2, and the proportion with improvement in neovascularization grades increased from 11.5% to 69.2%. Increases in the proportion of patients with improved neovascularization grades and the proportion who achieved IOP control (≤ 21 mmHg) were also observed by week 2 in this group. Overall, 77.8% and 74.1% of patients treated with IVT-AFL and sham/IVT-AFL, respectively, received a single IVT-AFL injection. The most common ocular treatment-emergent adverse event was punctate keratitis (9.3%: 7.4% and 11.1% in the IVT-AFL and sham/IVT-AFL groups, respectively).

Conclusions: IVT-AFL was associated with clinically meaningful improvements in IOP control, indicating that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma.

Trial Registration: Clinicaltrials.gov identifier, NCT02396316.
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http://dx.doi.org/10.1007/s12325-020-01579-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889669PMC
February 2021

Complete Visual Recovery From Severe Outer Retinitis After Tonsillitis.

J Neuroophthalmol 2020 Sep 11. Epub 2020 Sep 11.

Department of Ophthalmology (RK, KM, NH, KN), Osaka University Graduate School of Medicine, Osaka, Japan; Department of Ophthalmology (KK), Kindai University Faculty of Medicine, Osaka-Sayama City, Japan; Osaka University Graduate School of Frontier Biosciences (TF), Osaka, Japan; and Integrated Frontier Research for Medical Science Division (KN), Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan.

Background: To report a case of severe acute bilateral outer retinitis after tonsillitis and rapid morphologic and functional recovery after steroid treatment.

Methods: Observational case report.

Results: A 26-year-old woman with acute bilateral blurred vision that developed after tonsillitis underwent spectral-domain optical coherence tomography (SD-OCT) that showed photoreceptor outer segment damage. Full-field electroretinography (ERG) and multifocal ERG were nonrecordable. The patient had a remarkable anatomic and functional recovery in response to steroid treatment; however, partial damage remained around the macula on SD-OCT, and an adaptive optics imaging system showed damaged cone photoreceptors.

Conclusions: Prednisolone is an effective treatment for a disease that is believed to be due to suspicious involvement of the autoimmune system. Even severe outer retinitis can recover completely with rapid diagnosis and treatment.
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http://dx.doi.org/10.1097/WNO.0000000000001073DOI Listing
September 2020

Oral hypofunction and its association with frailty in community-dwelling older people.

Geriatr Gerontol Int 2020 Oct 23;20(10):917-926. Epub 2020 Aug 23.

Aichi Dental Association, Aichi, Japan.

Aim: This large epidemiological survey of older people examined oral hypofunction and the relationship between oral hypofunction and frailty.

Methods: Participants were community-dwelling adults aged 65-85 years in Japan. The oral function evaluation included seven items (oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory function and swallowing function), and oral hypofunction was defined as having abnormalities in at least three of these items. The frailty status was classified into three categories (robust, pre-frail and frail) according to the total Kihon Checklist score. We analyzed 978 subjects with complete data. The relationship between oral function and frailty status was analyzed using multivariate multinomial logistic regression analyses.

Results: Approximately 60% of the older adults had oral hypofunction. The multivariate odds ratios (ORs) for a pre-frail or frail status were significantly higher for older people with reduced occlusal force, reduced tongue-lip motor function and deteriorated swallowing function than in those without deterioration of those items. Of the oral function items, swallowing function was most strongly associated with the frailty status, and the ORs (95% confidence interval [CI]) for deteriorated swallowing function in pre-frail and frail patients were 6.4 (3.9-10.8) and 10.2 (5.4-19.1), respectively. Those with oral hypofunction had significantly higher adjusted ORs for pre-frail (OR 1.4, 95% CI 1.1-2.0) and frail (OR 2.1, 95% CI 1.2-3.5) statuses.

Conclusion: Many community-dwelling older people have reduced oral function or oral hypofunction, which is significantly associated with frailty in older people. Geriatr Gerontol Int 2020; 20: 917-926.
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http://dx.doi.org/10.1111/ggi.14015DOI Listing
October 2020

Analysis of Interaction Between Porphyromonas gingivalis and Endothelial Cells In Vitro.

Authors:
Kenji Matsushita

Methods Mol Biol 2021 ;2210:225-233

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.

Chronic periodontitis is the most common periodontitis observed in adults. Recently, its association with systemic diseases such as ischemic heart-brain disease and diabetes has been pointed out. Porphyromonas gingivalis, a major causative bacterium of chronic periodontitis, has properties of adhering to blood vessels and inducing inflammation, and those properties are involved in the induction of vascular inflammation and promotion of atherosclerosis. Therefore, analysis of the interaction of P. gingivalis with vascular endothelial cells will contribute to an understanding of the link between periodontitis and vascular lesions.
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http://dx.doi.org/10.1007/978-1-0716-0939-2_22DOI Listing
March 2021

Development of an Infrared Monitor-Guided Bleb Revision Procedure.

Case Rep Ophthalmol 2020 May-Aug;11(2):234-241. Epub 2020 Jun 25.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Suita, Japan.

The needle revision procedure to address failing filtering blebs is a blind technique that might easily damage the scleral flap, conjunctiva, and choroid. We propose a new surgical procedure, infrared monitor-guided bleb revision, to perform bleb revision minimally invasively and effectively, and demonstrate the procedure in a patient. We developed the guided procedure with the infrared monitor to observe the bleb interior with greater contrast. Under the monitor, we dissect the hard fibrotic tissue with a bleb knife and, if necessary, remove adhesions using a needle and vitreous forceps. Finally, 5-fluorouracil is injected into the subconjunctiva. We have performed bleb revisions safely with clear visualization of the scleral flap using an infrared light. In the current case, the patient had good intraocular pressure control for about 1 year. The new infrared monitor-guided bleb revision procedure facilitates successful bleb revisions without damage to the underlying structures.
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http://dx.doi.org/10.1159/000508606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383186PMC
June 2020

Assessment of a self-assembling peptide gel, SPG-178, in providing a clear operative field for trabeculectomy surgery for glaucoma in an animal model.

Sci Rep 2020 07 9;10(1):11326. Epub 2020 Jul 9.

Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.

The presence of blood during ophthalmic surgery is problematic, as it can obstruct a surgeon's view of the operative field. This is particularly true when performing trabeculectomy surgery to enhance ocular fluid outflow and reduce intraocular pressure as a treatment for glaucoma, one of the most common vision loss conditions worldwide. In this study, we investigated the performance of a transparent, self-assembling peptide gel (SPG-178) and its ability to maintain visibility during trabeculectomy surgery. Unlike the hyaluronic acid gel commonly used in ophthalmic surgery, SPG-178 did not permit the ingress of blood into the gel itself. Rather, it forced blood to flow peripherally to the gel. Moreover, if bleeding occurred under the SPG-178 gel, perfusion with saline was able to effectively flush the blood away along the interface between the SPG-178 and the ocular tissue (in this case scleral) to clear the surgical field of view. In experimental trabeculectomy surgeries with mitomycin C used as an adjuvant, there were no differences in the postoperative recovery of intraocular pressure or bleb morphology with or without the use of SPG-178. SPG-178, therefore, when used in a gel formulation, represents a new material for use in intraocular surgery to ensure a clear operative field with likely beneficial treatment outcomes.
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http://dx.doi.org/10.1038/s41598-020-68171-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347556PMC
July 2020

Periodontal Disease and Periodontal Disease-Related Bacteria Involved in the Pathogenesis of Alzheimer's Disease.

J Inflamm Res 2020 30;13:275-283. Epub 2020 Jun 30.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.

Alzheimer's disease (AD) is the most common cause of dementia, and it exhibits pathological properties such as deposition of extracellular amyloid β (Aβ) and abnormally phosphorylated Tau in nerve cells and a decrease of synapses. Conventionally, drugs targeting Aβ and its related molecules have been developed on the basis of the amyloid cascade hypothesis, but sufficient effects on the disease have not been obtained in past clinical trials. On the other hand, it has been pointed out that chronic inflammation and microbial infection in the brain may be involved in the pathogenesis of AD. Recently, attention has been focused on the relationship between the periodontopathic bacterium and AD. and its toxins have been detected in autopsy brain tissues from patients with AD. In addition, pathological conditions of AD are formed or exacerbated in mice infected with . Compounds that target the toxins of ameliorate the pathogenesis of AD triggered by infection. These findings indicate that the pathological condition of AD may be regulated by controlling the bacteria in the oral cavity and the body. In the current aging society, the importance of oral and periodontal care for preventing the onset of AD will increase.
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http://dx.doi.org/10.2147/JIR.S255309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335281PMC
June 2020

Quantitative Analysis of the Association Between Follow-Up Duration and Severity of Limbal Stem Cell Deficiency or Visual Acuity in Aniridia.

Invest Ophthalmol Vis Sci 2020 06;61(6):57

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Purpose: This study aimed to quantitatively analyze the association between follow-up duration and the severity of limbal stem cell deficiency (LSCD) or visual acuity in patients with aniridia.

Methods: A total of 52 eyes of 27 patients with aniridia were enrolled at Osaka University Hospital. Medical records were retrospectively reviewed to obtain information on the severity of LSCD and corrected distance visual acuity (CDVA). LSCD severity was based on a modified severity grading scale. We used an ordered logistic regression model to examine the association between follow-up duration and LSCD severity, and a linear regression model with a generalized linear mixed model for the association between follow-up duration and visual acuity.

Results: The mean follow-up duration was 5.2 ± 6.3 years. The mean age at the last follow-up visit was 40.5 ± 18.9 years. The mean CDVA was 1.52 ± 1.09 logMAR. At the last follow-up, 1 examined eye (1.9%) was categorized as stage 0, 7 (13.5%) as Ia, 9 (17.3%) as Ib, 5 (9.6%) as Ic, 2 (3.8%) as IIb, 12 (23.1%) as IIc, and 11 (21.2%) as III. Five eyes (9.6%) were unclassifiable. There was a significant association between follow-up duration and LSCD severity (odds ratio per +1 year, 1.41; P < 0.001). CDVA significantly decreased as follow-up duration increased. Each increase of 1 year in the follow-up duration was associated with a mean difference of +0.021 logMAR (95% confidence interval [CI] 0.01-0.03; P < 0.001).

Conclusion: We quantitatively demonstrate that LSCD severity and visual impairment significantly progress as follow-up duration increases.
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http://dx.doi.org/10.1167/iovs.61.6.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415892PMC
June 2020

Effect of peripapillary tilt direction and magnitude on central visual field defects in primary open-angle glaucoma with high myopia.

Jpn J Ophthalmol 2020 Jul 22;64(4):414-422. Epub 2020 Jun 22.

Department of Ophthalmology E7, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Purpose: To evaluate the relationship between peripapillary tilt and visual field (VF) defects in glaucomatous eyes with axial myopia.

Study Design: Retrospective cross-sectional study.

Patients And Methods: One hundred four eyes of 104 patients with primary open-angle glaucoma (POAG) with myopia were included (52 eyes with high myopia [HM], 26.5 mm ≤ axial length [AL] < 30.0 mm; and 52 eyes without HM, 24.0 mm < AL < 26.5 mm). The direction and magnitude of the peripapillary tilt were evaluated using optical coherence tomography. The eyes were divided into 12 groups according to the tilt directions defined by clock-hour sectors in a clockwise direction in the right eyes and in a counterclockwise direction in the left eyes. The mean deviation (MD) and central VF (CVF) values, ie, the mean threshold values of 4 paracentral points within 5 degrees of the Swedish Interactive Threshold Algorithm 30-2 test, were evaluated.

Results: The direction of the tilt was toward sector 9 (47.1%) and sector 8 (34.6%). The MD and CVF values were significantly worse (P = 0.013 and P = 0.019, respectively) in the sector 9 group than in the sector 8 group. Furthermore, the smaller peripapillary tilt magnitude in the sector 9 group was negatively correlated (P = 0.0019) with the CVF but not with the MD (P = 0.1) among the POAG eyes with HM. In contrast, the ovality index in the sector 9 group was not significantly correlated with the MD (P = 0.4) or the CVF (P = 0.36).

Conclusion: A smaller temporal peripapillary tilt correlated with CVF defects in POAG eyes with HM. The peripapillary tilt direction and magnitude affect the CVF defect in POAG eyes with HM.
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http://dx.doi.org/10.1007/s10384-020-00747-yDOI Listing
July 2020

Synthetic cell-permeable caveolin-1 scaffolding domain peptide activates phagocytosis of Escherichia coli by regulating Rab5 activity.

Z Naturforsch C J Biosci 2020 Sep;75(9-10):333-337

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, 7-430 Morioka, 474-8522, Obu, Aichi, Japan.

Caveolae are defined as 50-100 nm wide pits in the plasma membrane containing oligomeric caveolin proteins. They have been implicated in endocytosis (including phagocytosis), transcytosis, calcium signalling, and numerous other signal transduction events. Caveolin-1, a major structural component of caveolae, enhances Rab5 activity. In this study, we examined the effect of a synthetic cell-permeable peptide of the caveolin-1 scaffolding domain (CSD) on phagocytosis. Treatment with the CSD peptide increased Rab5 activity, Rab5-early endosome antigen 1 (EEA1) interaction, and phagocytosis of Escherichia coli. The results suggest that the synthetic cell-permeable CSD peptide is an activator of phagocytosis.
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http://dx.doi.org/10.1515/znc-2020-0023DOI Listing
September 2020

High concentration of glucose induces filaggrin-1 expression through AP-1 in skin keratinocytes.

J Dermatol Sci 2020 May 14;98(2):137-140. Epub 2020 Apr 14.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2020.04.002DOI Listing
May 2020

Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese.

Clin Exp Ophthalmol 2020 07 24;48(5):658-665. Epub 2020 Mar 24.

Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.

Background: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese.

Methods: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis.

Results: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P = .0019, OR = 4.55, I = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P = .81, OR = 1.05; I = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects.

Conclusions: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.
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http://dx.doi.org/10.1111/ceo.13744DOI Listing
July 2020

Transient changes in refractive error and corneal tomography after 24-h continuous monitoring of intraocular pressure patterns with a contact lens sensor.

Jpn J Ophthalmol 2020 Mar 13;64(2):127-133. Epub 2020 Feb 13.

Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan.

Purpose: To evaluate changes in refractive error and corneal tomographic measurements after 24-h monitoring of intraocular pressure patterns with a contact lens sensor (CLS).

Study Design: Prospective, longitudinal, observational study.

Patients And Methods: Fourteen eyes of 14 consecutive patients who underwent 24-h CLS monitoring were enrolled. The objective spherical equivalent (SE) refractive error was measured using automated refraction and keratometry. The axial power, instantaneous power, and corneal thickness at the central, paracentral, midperipheral, and peripheral cornea were measured with swept-source anterior-segment optical coherence tomography. Measurements were performed at baseline, immediately after monitoring, and at follow-up visits 2-4 days after monitoring.

Results: The myopic SE increased significantly (P < 0.001) from - 5.1 ± 4.2 to - 6.0 ± 4.0, D after 24-h monitoring with a CLS and returned to the premonitoring level at the second visit (- 5.3 ± 4.4 D, P = 0.315). Decreases in the midperipheral and peripheral axial powers and the paracentral instantaneous power and increases in the central instantaneous power and peripheral corneal thickness occurred after CLS monitoring.

Conclusion: Twenty-four-hour monitoring with a CLS resulted in significant increases in the myopic refractive error and corneal central steepening and midperipheral flattening. Although these changes are transient and do not negate the clinical merits of the CLS, clinicians should be aware of these potential adverse events. Three-dimensional evaluation of corneal deformation with anterior segment optical coherence tomography is a powerful tool for assessing and improving the safety, tolerability, and accuracy of CLS devices.
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http://dx.doi.org/10.1007/s10384-020-00723-6DOI Listing
March 2020

Histone H3K9 methylation is involved in temporomandibular joint osteoarthritis.

Int J Mol Med 2020 Feb 27;45(2):607-614. Epub 2019 Dec 27.

Crown and Bridge Prosthodontics, Department of Oral Functional Science, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Hokkaido 060‑8586, Japan.

The morbidity of temporomandibular joint osteoarthritis (TMJOA) increases with age. Condylar articular cartilage degradation, which causes TMJOA, is known to be involved in articular chondrocyte metabolic imbalances in the temporomandibular joint (TMJ) and in other joints of the body. Epigenetic regulation, such as the chemical modification of DNA and histones, is implicated in cartilage homeostasis. However, few studies have been conducted on the epigenetic regulation of condylar articular cartilage degradation. The present study investigated the regulation of histone H3 lysine 9 (H3K9) methylation and its effects on the pathogenesis of degenerative TMJ cartilage disorders. The histone H3K9 methylation level was decreased in degenerated condylar articular cartilage in aged mice. Treatment with chaetocin (a selective H3K9 methylation inhibitor) reduced cell viability and promoted caspase‑3/7 activity in ATDC5 mouse chondroprogenitor cells. The inhibition of H3K9 methylation increased matrix metalloproteinase (Mmp)1 and Mmp13 mRNA expression in these cells. Furthermore, the expression levels of Sox9 and collagen α1(II) (Col2a1) mRNA, which are anabolic factors for chondrogenic differentiation, were also decreased by treatment with chaetocin, which is an inhibitor of histone methyltransferases. These results indicated that histone H3K9 methylation regulates chondrocyte homeostasis in terms of cell growth, apoptosis and gene expression, and highlighted a possible future therapy option for TMJOA.
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http://dx.doi.org/10.3892/ijmm.2019.4446DOI Listing
February 2020

Deep learning based noise reduction method for automatic 3D segmentation of the anterior of lamina cribrosa in optical coherence tomography volumetric scans.

Biomed Opt Express 2019 Nov 21;10(11):5832-5851. Epub 2019 Oct 21.

Topcon Advanced Biomedical Imaging Laboratory, Oakland, NJ 07436, USA.

A deep-learning (DL) based noise reduction algorithm, in combination with a vessel shadow compensation method and a three-dimensional (3D) segmentation technique, has been developed to achieve, to the authors best knowledge, the first automatic segmentation of the anterior surface of the lamina cribrosa (LC) in volumetric ophthalmic optical coherence tomography (OCT) scans. The present DL-based OCT noise reduction algorithm was trained without the need of noise-free ground truth images by utilizing the latest development in deep learning of de-noising from single noisy images, and was demonstrated to be able to cover more locations in the retina and disease cases of different types to achieve high robustness. Compared with the original single OCT images, a 6.6 dB improvement in peak signal-to-noise ratio and a 0.65 improvement in the structural similarity index were achieved. The vessel shadow compensation method analyzes the energy profile in each A-line and automatically compensates the pixel intensity of locations underneath the detected blood vessel. Combining the noise reduction algorithm and the shadow compensation and contrast enhancement technique, medical experts were able to identify the anterior surface of the LC in 98.3% of the OCT images. The 3D segmentation algorithm employs a two-round procedure based on gradients information and information from neighboring images. An accuracy of 90.6% was achieved in a validation study involving 180 individual B-scans from 36 subjects, compared to 64.4% in raw images. This imaging and analysis strategy enables the first automatic complete view of the anterior LC surface, to the authors best knowledge, which may have the potentials in new LC parameters development for glaucoma diagnosis and management.
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http://dx.doi.org/10.1364/BOE.10.005832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865099PMC
November 2019

Involvement of adiponectin in age-related increases in tear production in mice.

Aging (Albany NY) 2019 10 8;11(19):8329-8346. Epub 2019 Oct 8.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu 474-8511, Japan.

Common age-related changes in the human eye contribute to the development of dry eye, including decreases in aqueous tear production. Although the infiltration of lymphocytes into the lacrimal glands occurs with age, age-related increases in tear production have also been observed in mice; however, the mechanisms underlying this increase remain unclear. We herein demonstrated that increases in tear production were not dependent on body weight gain or systemic conditions, such as insulin resistance, using aged mice and high-fat diet-fed mice. The results obtained also showed that senescence-associated T (SA-T) cells accumulated in the lacrimal glands of aged mice, particularly females. Expression levels of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) in whole lacrimal glands and epithelial cells isolated from lacrimal glands were significantly higher in aged mice than in young mice. The expression levels of adiponectin and one of its receptors, AdipoR2, also increased in the lacrimal glands of aged mice, but not in those of high-fat diet-fed mice. Collectively, the present results indicate that PPARγ and adiponectin-mediated signaling contribute to age-related increases in tear production in mice and have potential as therapeutic targets for the treatment of dry eye in humans.
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http://dx.doi.org/10.18632/aging.102322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814586PMC
October 2019

Transient extremely shallow anterior chamber caused by ciliochoroidal detachment in a patient with keratitis.

Am J Ophthalmol Case Rep 2019 Sep 1;15:100530. Epub 2019 Aug 1.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Purpose: To report a case of keratitis that resulted in a transient reduction of anterior chamber depth.

Observations: A 46-year-old man with keratoconus and reduced visual acuity (20/286) in his left eye presented with ciliary injection 16 months after femtosecond laser-assisted penetrating keratoplasty (PK). A slit-lamp examination showed a corneal ulcer with infiltrates and edema in both the host and graft between the 3 o'clock and 6 o'clock positions. Microbiologic tests confirmed the presence of . Topical arbekacin and moxifloxacin, erythromycin/colistin ointment, and oral clarithromycin were prescribed. We monitored anterior chamber depth by anterior segment optical coherence tomography (AS-OCT) throughout the recovery period. The anterior chamber depth was normal before treatment, with an intraocular pressure (IOP) of 7 mmHg. Although ciliary injection and infiltrates were gradually resolved, slit-lamp examination and AS-OCT revealed an extreme reduction of anterior chamber depth without corneal perforation, 1 month after beginning treatment. The IOP was 5 mmHg, and ciliochoroidal detachment (CCD) was present. The anterior chamber increased with the resolution of CCD and keratitis. Although hypotony continued despite the resolution of CCD and keratitis, the IOP eventually recovered to ≥10 mmHg at 1 month after remission. Onset and resolution of transient reduction of anterior chamber depth presumably occurred by anterior rotation and recovery of the ciliary body, respectively. Subsequent PK triple surgery enabled visual recovery to 20/100.

Conclusions And Importance: severe anterior segment inflammation due to infectious keratitis may cause CCD and subsequent reduction of anterior chamber depth due to anterior rotation. AS-OCT is a non-invasive and efficient tool for the evaluation of iridociliary structure and the anterior chamber in patients with infectious keratitis.
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http://dx.doi.org/10.1016/j.ajoc.2019.100530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690428PMC
September 2019

Lattice corneal dystrophy with familial amyloid polyneuropathy.

Int J Clin Pract 2019 06 25;73(6):e13320. Epub 2019 Feb 25.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1111/ijcp.13320DOI Listing
June 2019

Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese.

Exp Eye Res 2019 03 23;180:129-136. Epub 2018 Dec 23.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China. Electronic address:

The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (P = 4.3 × 10, OR = 0.72, I = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P = 0.0061, OR = 0.69, I = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (P = 0.017, OR = 0.70, I = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P<0.005). Furthermore, two haplotypes, C-C (P = 1.13 × 10, OR = 1.41, I = 0) and A-A (P = 0.045, OR = 0.68, I = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.
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http://dx.doi.org/10.1016/j.exer.2018.12.014DOI Listing
March 2019

Cross-Sectional Imaging Analysis of Epiretinal Membrane Involvement in Unilateral Open-Angle Glaucoma Severity.

Invest Ophthalmol Vis Sci 2018 12;59(15):5745-5751

Department of Ophthalmology, Osaka University Graduate School of Medicine, Yamadaoka, Japan.

Purpose: To determine the relevance of epiretinal membranes (ERMs) in primary open-angle glaucoma (POAG) and potential risk for glaucoma severity.

Methods: Sixty eyes of 30 patients with POAG who had a unilateral ERM were analyzed; 60 nonglaucomatous eyes of 30 patients with a unilateral ERM also were recruited in this institutional cross-sectional study. Patients underwent swept-source (SS) optical coherence tomography (OCT) imaging and visual field testing. Intraindividual differences in the SS-OCT retinal nerve fiber layer (RNFL) disc cupping area measurements and visual field outcomes were analyzed in the two groups.

Results: In patients with POAG, the mean circumpapillary RNFL thickness in the eyes with an ERM was 75.6 ± 16.5 μm superiorly and 71.8 ± 26.0 inferiorly compared with the fellow eyes without an ERM (87.2 ± 23.6 μm, P = 0.0061 and 81.3 ± 27.7 μm, P = 0.034, respectively). The areas of disc cupping and cup-to-disc ratio seen on OCT horizontal and vertical B-scans were larger in eyes with an ERM than in the fellow eyes without ERM (P = 0.0004 and P = 0.0011, respectively). The average mean deviations were -11.6 ± 7.5 dB in the ERM group and -8.19 ± 6.4 dB in the group with no ERM (P = 0.029). Eyes with an ERM received more antiglaucoma eye drops (P = 0.018). Those differences were not seen between eyes with an ERM or fellow eyes in patients without glaucoma.

Conclusions: The presence of an ERM can be a potential risk factor for unilateral severity in eyes with POAG.
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http://dx.doi.org/10.1167/iovs.18-25292DOI Listing
December 2018

Contribution of Bipolar Cells of Cone ON and OFF Pathways to Electroretinograms Elicited by Ultraviolet and Middle Wavelength Stimuli.

Curr Eye Res 2019 04 4;44(4):413-422. Epub 2018 Dec 4.

a Department of Ophthalmology , Osaka University Graduate School of Medicine , Osaka , Japan.

Purpose: To determine the contribution of the ON and OFF cone bipolar cell pathways to the electroretinograms (ERGs) elicited by ultraviolet (UV) and middle wavelength light in mice.

Materials And Methods: The experiments were performed on 8- to 10-week-old C57BL/6J mice. The ERGs elicited by single-flash and flickering UV light stimuli were compared to those elicited by green light stimuli under photopic conditions. Pharmacological agents were used to selectively block the ON and OFF pathways contributing to the ERGs. Saline was used as a control. The flicker ERGs elicited by UV light were compared to the ERGs elicited by green light after the injection of the pharmacological agents to determine the contribution of the cone ON and OFF pathways to the ERGs.

Results: The photopic single-flash and flicker ERGs were more sensitive to the UV light stimuli than to those elicited by green light stimuli. The flicker ERG responses elicited by both UV and green light stimuli at stimulus frequencies lower than 15-Hz decreased after L-2-amino-4-phosphobutyric acid was injected. The ERGs elicited by UV light at 30-Hz and by green light at frequencies lower than 15-Hz decreased significantly after the intravitreal injection of cis-2, 3-piperidine-dicarboxylic acid. An analysis of the ON and OFF components of the flicker ERGs showed that there might be pharmacological differences between the UV light-sensitive responses and the green light-sensitive responses.

Conclusions: These results suggest that the UV light-sensitive cones connect to both the ON and OFF bipolar cells differently than that of the green light-sensitive cones.
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http://dx.doi.org/10.1080/02713683.2018.1549262DOI Listing
April 2019

Porphyromonas gingivalis induces the production of interleukin-31 by human mast cells, resulting in dysfunction of the gingival epithelial barrier.

Cell Microbiol 2019 03 28;21(3):e12972. Epub 2018 Nov 28.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.

Interleukin (IL)-31 is important for innate immunity in mucosal tissues and skin, and increased IL-31 expression participates in the pathogenesis of chronic inflammatory diseases affecting the skin, airways, lungs, and intestines. We investigated the contribution of mast cells to the induction of IL-31 production following infection with the periodontal pathogen, Porphyromonas gingivalis. We found that oral infection with P. gingivalis increased IL-31 expression in the gingival tissues of wild-type mice but not in those of mast cell-deficient mice. The P. gingivalis-induced IL-31 production by human mast cells occurred through the activation of the JNK and NF-κB signalling pathways and was dependent on the P. gingivalis lysine-specific protease gingipain-K. P. gingivalis infection induced IL-31 receptor α and oncostatin M receptor β expression in human gingival epithelial cells. Notably, the P. gingivalis-induced IL-31 production by mast cells led to the downregulation of claudin-1, a tight junction molecule, in gingival epithelial cells, resulting in an IL-31-dependent increase in the paracellular permeability of the gingival epithelial barrier. These findings suggest that IL-31 produced by mast cells in response to P. gingivalis infection causes gingival epithelial barrier dysfunction, which may contribute to the chronic inflammation observed in periodontitis.
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http://dx.doi.org/10.1111/cmi.12972DOI Listing
March 2019

Anterior segment Scheimpflug imaging for detecting primary angle closure disease.

Graefes Arch Clin Exp Ophthalmol 2019 Jan 30;257(1):161-167. Epub 2018 Oct 30.

Department of Ophthalmology, Graduate School of Medicine, Osaka University, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan.

Purpose: To evaluate the capability of anterior segment Scheimpflug imaging for detecting primary angle closure disease (PACD): primary angle closure suspect, primary angle closure, and primary angle closure glaucoma, using cutoff points derived from reference databases of healthy subjects.

Methods: Eighty-seven patients with PACD and 49 age-matched control subjects were included. We evaluated the sensitivity and specificity of anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) to differentiate patients with PACD from controls. Additionally, the study's raw data was analyzed via receiver operating characteristic curves for comparison.

Results: One standard deviation from the normative data's mean values was used as the cutoff point and yielded a sensitivity and specificity of 96.2% and 92.6% for ACD, 97.1% and 75.9% for ACV, and 93.3% and 72.2% for ACA, respectively. Receiver operating characteristic analysis of the raw data showed the area under the curve to be 0.984, 0.975, and 0.931 for ACD, ACV, and ACA, respectively.

Conclusions: Our study demonstrated that the parameters of anterior segment Scheimpflug imaging, particularly ACD, accurately discriminate PACD. This was the first study to validate the device's normative data in a separate population. With its high reproducibility, ease of use, non-invasiveness, and speed, anterior segment Scheimpflug imaging is a potentially powerful screening tool for PACD.
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http://dx.doi.org/10.1007/s00417-018-4171-xDOI Listing
January 2019

Factors affecting the appetites of persons with Alzheimer's disease and mild cognitive impairment.

Geriatr Gerontol Int 2018 Aug 29;18(8):1236-1243. Epub 2018 May 29.

Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Obu, Japan.

Aim: Appetite loss has been associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Among older people, decreased appetite can result in poor nutrition and subsequent loss of independent living. We examined the factors related to appetite loss in persons with AD and MCI to provide evidence for countermeasures to prevent appetite loss and progression of cognitive impairment.

Methods: We included 1238 older adults undergoing outpatient treatment at the Center for Comprehensive Care and Research on Memory Disorders (Medical Center for Dementia) at the National Center for Geriatrics and Gerontology in Obu, Japan. The Council on Nutrition Appetite Questionnaire, an appetite questionnaire for older people, was used to evaluate appetite. Appetite loss in persons diagnosed with AD or MCI was divided into two groups according to the Council on Nutrition Appetite Questionnaire scores, and logistic regression analysis was carried out to identify independent factors associated with appetite loss. The following variables were used to evaluate for covariates: general information, functional evaluation and medications.

Results: The AD and MCI groups contained 853 and 385 individuals, respectively. In both groups, depression and difficulty in maintaining attention while eating were significantly associated with poor appetite. Among persons with AD, lower vitality, more comorbidities, non-use of antidementia drugs and use of psychotropic drugs were also significantly associated with poor appetite.

Conclusions: The present study recognized possible factors individually associated with appetite loss among persons with AD or MCI. Future studies are required to examine supportive strategies to treat poor appetite in these populations. Geriatr Gerontol Int 2018; 18: 1236-1243.
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http://dx.doi.org/10.1111/ggi.13455DOI Listing
August 2018

Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity.

Cell Rep 2018 03;22(13):3548-3561

Laboratory for Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address:

In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function.
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http://dx.doi.org/10.1016/j.celrep.2018.03.007DOI Listing
March 2018

Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.

NPJ Aging Mech Dis 2017 6;3:15. Epub 2017 Nov 6.

Department of Oral Disease Research, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, 474-8511 Japan.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as . Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of -inoculated mice. LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.
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http://dx.doi.org/10.1038/s41514-017-0015-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673943PMC
November 2017