TLR2 Supports γδ T cell IL-17A Response to ocular surface commensals by Metabolic Reprogramming.

The ocular surface is a mucosal barrier tissue colonized by commensal microbes, which tune local immunity by eliciting IL-17 from conjunctival γδ T cells to prevent pathogenic infection. The commensal () elicits protective IL-17 responses from conjunctival Vγ4 T cells through a combination of γδ TCR ligation and IL-1 signaling. Here, we identify Vγ6 T cells as a major -responsive subset in the conjunctiva and uncover its unique activation requirements.

Too Much of a Good Thing: Extended Duration of Gut Microbiota Depletion Reverses Protection From Experimental Autoimmune Uveitis.

Purpose: Using the model of experimental autoimmune uveitis (EAU) induced by immunization with a retinal antigen, two studies have reported contradictory results on disease development following oral antibiotic treatment (ABX). We showed that long-term ABX did not affect EAU, but another study showed that short-term ABX was protective. We therefore studied the effects of ABX on EAU, gut microbiota, and host immune responses as a function of treatment duration.

Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation.

The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling.

Flexural and Cell Adhesion Characteristic of Phakic Implantable Lenses.

: In this study, we aimed to compare the physical properties of hole-implantable collamer lenses (H-ICLs) and implantable phakic contact lenses (IPCLs) and investigate their flexural and cell adhesion characteristics. : Transverse compression load to achieve lens flexion and static Young's modulus were measured in H-ICLs and IPCLs using designated equipment. Load was measured both with and without restraining the optic section of the lenses.

Evaluation of long-term clinical outcomes after toric implantable collamer lens implantation.

Purpose: To evaluate the long-term (8-10 years) outcomes of toric implantable collamer lens (TICL) surgery.

Setting: Nagoya Eye Clinic, Nagoya, Aichi, Japan.

Design: Retrospective observational study.

Age-related changes of color visual acuity in normal eyes.

Purpose: To evaluate the age-related change in color visual acuity (CVA) in normal eyes.

Methods: In total, 162 normal eyes (162 subjects, women: 52, men: 110, age range: 15-68 years) with best-corrected visual acuity (BCVA) ≥20/13 were enrolled. Fifteen colors from the New Color Test (chroma 6) were applied to Landolt "C" rings, white point D65 was applied as background, and a luminance of 30 cd/m2 was set for both the rings and the background.

Splenic Volume Index Determined Using Computed Tomography upon Admission Is Associated with Readmission for Heart Failure Among Patients with Acute Decompensated Heart Failure.

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission.

Microbiota as Drivers and as Therapeutic Targets in Ocular and Tissue Specific Autoimmunity.

Autoimmune uveitis is a major cause of blindness in humans. Activation of retina-specific autoreactive T cells by commensal microbiota has been shown to trigger uveitis in mice. Although a culprit microbe and/or its immunogenic antigen remains to be identified, studies from inducible and spontaneous mouse models suggest the potential of microbiota-modulating therapies for treating ocular autoimmune disease.

Regulated Tristetraprolin Overexpression Dampens the Development and Pathogenesis of Experimental Autoimmune Uveitis.

Non-infectious uveitis, a common cause of blindness in man, is often mediated by autoimmunity, a process in which cytokines play major roles. The biosynthesis and secretion of pro-inflammatory cytokines are regulated in part by tristetraprolin (TTP), an endogenous anti-inflammatory protein that acts by binding directly to specific sequence motifs in the 3'-untranslated regions of target mRNAs, promoting their turnover, and inhibiting synthesis of their encoded proteins. We recently developed a TTP-overexpressing mouse (TTPΔARE) by deleting an AU-rich element (ARE) instability motif from the TTP mRNA, resulting in increased accumulation of TTP mRNA and protein throughout the animal.

T cell-intrinsic role for Nod2 in protection against Th17-mediated uveitis.

Mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) cause Blau syndrome, an inflammatory disorder characterized by uveitis. The antimicrobial functions of Nod2 are well-established, yet the cellular mechanisms by which dysregulated Nod2 causes uveitis remain unknown. Here, we report a non-conventional, T cell-intrinsic function for Nod2 in suppression of Th17 immunity and experimental uveitis.

The Cytokine IL-17A Limits Th17 Pathogenicity via a Negative Feedback Loop Driven by Autocrine Induction of IL-24.

Dysregulated Th17 cell responses underlie multiple inflammatory and autoimmune diseases, including autoimmune uveitis and its animal model, EAU. However, clinical trials targeting IL-17A in uveitis were not successful. Here, we report that Th17 cells were regulated by their own signature cytokine, IL-17A.

Autoimmunity to neuroretina in the concurrent absence of IFN-γ and IL-17A is mediated by a GM-CSF-driven eosinophilic inflammation.

IFN-γ and IL-17A can each elicit ocular autoimmunity independently of the other. Since absence of IFN-γ or IL-17A individually failed to abolish pathology of experimental autoimmune uveitis (EAU), we examined EAU development in the absence of both these cytokines. IfngIl17a mice were fully susceptible to EAU with a characteristic eosinophilic ocular infiltrate, as opposed to a mononuclear infiltrate in WT mice.

A novel role for lipoxin A in driving a lymph node-eye axis that controls autoimmunity to the neuroretina.

The eicosanoid lipoxin A (LXA) has emerging roles in lymphocyte-driven diseases. We identified reduced LXA levels in posterior segment uveitis patients and investigated the role of LXA in the pathogenesis of experimental autoimmune uveitis (EAU). Immunization for EAU with a retinal self-antigen caused selective downregulation of LXA in lymph nodes draining the site of immunization, while at the same time amplifying LXA in the inflamed target tissue.

AS101 ameliorates experimental autoimmune uveitis by regulating Th1 and Th17 responses and inducing Treg cells.

AS101 is an organotellurium compound with multifaceted immunoregulatory properties that is remarkable for its lack of toxicity. We tested the therapeutic effect of AS101 in experimental autoimmune uveitis (EAU), a model for human autoimmune uveitis. Unexpectedly, treatment with AS101 elicited Treg generation in vivo in otherwise unmanipulated mice.

Microbiome and Autoimmune Uveitis.

Commensal microbes affect all aspects of immune development and homeostasis in health and disease. Increasing evidence points to the notion that the gut commensals impact not only intestinal diseases but also diseases in tissues distant from the gut. Autoimmune or non-infectious uveitis is a sight-threatening intraocular inflammation that affects the neuroretina.

Control-matched comparison of refractive and visual outcomes between small incision lenticule extraction and femtosecond laser-assisted LASIK.

Purpose: This retrospective case-matched study aimed to compare visual and refractive outcomes between small incision lenticule extraction (SMILE) and LASIK.

Patients And Methods: Patients who underwent SMILE (34 eyes of 23 patients) or LASIK (34 eyes of 24 patients) were enrolled and matched according to preoperative manifest refractive spherical equivalents. The mean preoperative manifest refractive spherical equivalent was -4.

New surgical approach for intrascleral fixation using an intraocular lens with hook-shaped haptics.

We report a new surgical technique of intrascleral posterior chamber intraocular lens (PC IOL) fixation using a newly developed hook-shaped haptic IOL (NX-70CH) and a 25-gauge loop-shaped haptic manipulator. Previous techniques of intrascleral PC IOL fixation had 2 major technical challenges; that is, externalization of the haptic and fixation of the haptic into the scleral tunnel. The new IOL and manipulator can facilitate externalization and secure fixation of the IOL haptic and can be used for suture fixation or implantation in the capsular bag in cases with presumed subluxated lens.

STAT-3-independent production of IL-17 by mouse innate-like αβ T cells controls ocular infection.

Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4 T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αβ+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3.

Clinical and ex vivo laboratory comparison of the self-sealing properties and dimensional stability between the femtosecond laser and manual clear corneal incisions.

Purpose: To compare the self-sealing features and dimensional stability between the femtosecond laser (FL) and manual knife corneal incision.

Methods: For the clinical study, 29 consecutive eyes from 29 patients and 28 eyes from 28 patients who underwent cataract surgery with FL corneal incision and manual knife incision, respectively, were enrolled. Immediately after cataract surgery, the self-sealing features of the corneal incisions were evaluated.

Effect of Background Luminance Level on the Assessment of Color Visual Acuity Using Colored Landolt Rings in Young Healthy Subjects.

Purpose: To evaluate the color visual acuity (CVA) of young healthy subjects using colored Landolt rings and the effect of background luminance level on the CVA.

Materials And Methods: We measured the CVA of 20 young healthy subjects (age: 23.8 ± 3.

Comparison of Maximum Stretch Forces between Femtosecond Laser-Assisted Capsulotomy and Continuous Curvilinear Capsulorhexis.

The current study reports comparing the postoperative mechanical properties of the anterior capsule between femtosecond laser capsulotomy (FLC) and continuous curvilinear capsulorhexis (CCC) of variable size and shape in porcine eyes. All CCCs were created using capsule forceps. Irregular or eccentric CCCs were also created to simulate real cataract surgery.

Preparation of Protein-containing Extracts from Microbiota-rich Intestinal Contents.

The contribution of microbiota in regulating multiple physiological and pathological host responses has been studied intensively in recent years. Evidence suggests that commensal microbiota can directly modulate different populations of cells of the immune system (e.g.

Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site.

Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology.