Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

Behçet's disease is a systemic vasculitis of unknown etiology characterized by recurrent oral and genital ulcers and uveitis. The vascular involvement of Behçet's disease affects arteries, veins, and blood vessels of all sizes, and it can include venous or arterial thrombosis and arterial aneurysms. There are only a few reports of an aortic aneurysm invading a vertebral body in a patient with Behçet's disease. Here, we report the case of a 45-year-old man who was initially diagnosed with vertebral invasion of a mycotic aneurysm. He underwent vascular surgery and received empirical antibiotics, but all cultures were negative. However, he had persistent, recurrent deep vein thrombosis and elevated inflammatory markers. After reviewing the pathology, a final diagnosis of Behçet's disease was made. He was successfully treated with corticosteroids. This report presents a rare case of Behçet's disease mimicking vertebral invasion of a mycotic aneurysm.
Adrenal Cortex Hormones ; Aneurysm ; Aneurysm, Infected* ; Anti-Bacterial Agents ; Aortic Aneurysm ; Arteries ; Behcet Syndrome ; Blood Vessels ; Diagnosis ; Humans ; Middle Aged ; Osteomyelitis ; Pathology ; Systemic Vasculitis ; Thrombosis ; Ulcer ; Uveitis ; Veins ; Venous Thrombosis

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.
Humans ; Immunosuppression ; methods ; Immunosuppressive Agents ; therapeutic use ; Uveitis ; immunology ; pathology ; therapy

OBJECTIVETo study the influence of Yanyankang powder on Th1/Th2 in rats with experimental autoimmune uveitis (EAU).

METHODSThe EAU models were induced in Lewis rats by immunization with interphotoreceptor retinoid binding protein (IRBP) 1177-1191 in complete Freund's adjuvant. The rats were randomly divided into 3 groups: a model control group, a Yanyankang group, and a prednisone group, 9 rats in each group. The model control group was intervened with saline solution by gavage. The Yanyankang group was intervened with Yanyankang powder 4 g/(kg day) by gavage. The prednisone group were intervened with prednisone acetate tablets 5 mg/(kg d) by gavage. All groups were intervened after immunization once every 2 days for 18 days and monitored by slit-lamp biomicroscopy daily until day 18. The levels of gamma interferon (INF-γ) and interleukin-10 (IL-10) in the supernatants of T cells were determined by enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) technology was used for measuring Th1 and Th2 related cytokine mRNA expressions.

RESULTSSlighter intraocular inflammation was found in the Yanyankang group and the prednisone group than the control group. The levels of the IFN-γ and IL-10 in the supernatants of the spleen lymph node cells were 382.33±6.30, 155.87±4.46 μg/L in the Yanyankang group and 270.93±7.76, 265.32±11.88 μg/L in the prednisone group. Both had significant differences compared with the control group (941.53±8.59, 20.67±4.65 μg/L; =0.01). The PCR results showed the same tendency.

CONCLUSIONYanyankang powder showed favorable effects in the rats with EAU by influencing the function of Th1 and Th2 cells.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Eye ; pathology ; Female ; Immunization ; Inflammation ; pathology ; Interferon-gamma ; genetics ; metabolism ; Interleukin-10 ; genetics ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Powders ; RNA, Messenger ; genetics ; metabolism ; Rats, Inbred Lew ; Spleen ; metabolism ; Th1 Cells ; drug effects ; immunology ; Th2 Cells ; drug effects ; immunology ; Uveitis ; drug therapy ; genetics ; immunology

The authors wish to report a case of bilateral acute anterior uveitis and optic disc edema following a hemotoxic snake bite, in order to highlight the concomitant occurrence of these conditions and the potential adverse effects of anti-snake venom (ASV). A 35-year-old male was bitten by a viper at seventeen thirty hours, and was started on ASV. Two days following treatment he experienced sudden onset redness and painful diminution of vision in both eyes (OU). On examination, the patient's visual acuity (VA) in OU was 20/200. Examination revealed fresh keratic precipitates, cells, and flare in the anterior chamber (AC), posterior synechiae, sluggish and ill-sustained pupillary reaction, and hyperemic, edematous disc with blurred margins in OU. He was started on topical steroids, cycloplegics and intravenous methylprednisolone. Following treatment, the patient showed improvement and was continued on topical medications and oral prednisolone tapered over 3 weeks, after which VA OU improved, the AC showed no cells and flare and disc edema resolved. Uveitis and optic disc edema in snake bite can either be due to the direct toxic effects of the venom or the effect of ASV. Steroids have a beneficial role in the management of these symptoms.
Acute Disease ; Adult ; Antivenins/*adverse effects ; Glucocorticoids/administration & dosage ; Humans ; Hyperemia/drug therapy/etiology/pathology ; Male ; Methylprednisolone/administration & dosage ; Papilledema/drug therapy/*etiology/pathology ; Snake Bites/*complications/*therapy ; Uveitis, Anterior/drug therapy/*etiology/pathology

We report here the records of 10 consecutive Korean patients (10 eyes) with ocular toxoplasmosis which showed the typical clinical manifestations with seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA between 2006 and 2010. Nine patients were males and 1 was female; their age was 50.5+/-13.8 years. The most common accompanying signs were vitritis (100%), anterior uveitis (70%), and scattered white deposit (80%). Pre-existing retinochoroidal scar was found in 1 (10%) patient. All patients received antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved the presenting attack and recovered the visual acuity better than initial one in 9 patients and worse in 1. Optic atrophy, cataract, and retinal neovascularization were observed during the follow-up period and recurrence was detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea, although rarely detected and reported, ocular toxoplasmosis needs more attention in clinical field of retinal diseases.
Adrenal Cortex Hormones/administration & dosage ; Adult ; Age Distribution ; Aged ; Anti-Inflammatory Agents/administration & dosage ; Antibodies, Protozoan/*blood ; Antiprotozoal Agents/administration & dosage ; Cataract/pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin G/blood ; Korea ; Male ; Middle Aged ; Optic Atrophy/pathology ; Retinal Neovascularization/pathology ; Sex Distribution ; Toxoplasma/immunology/*isolation & purification ; Toxoplasmosis, Ocular/complications/*diagnosis/drug therapy/*pathology ; Uveitis, Anterior/complications/drug therapy/parasitology/pathology

A 60-year-old male was referred to the ophthalmologic clinic with aggravated anterior uveitis and corneal edema despite the use of topical and systemic steroids. He had undergone cataract surgery in both eyes 15 years previous. Slit lamp examinations revealed a retained lens fragment in the inferior angle of the anterior chamber, with severe corneal edema and mild anterior uveitis. The corneal edema and uveitis subsided following surgical extraction of the lens fragment. That a retained lens fragment caused symptomatic anterior uveitis with corneal edema 15 years after an uneventful cataract surgery is unique. A retained lens fragment should be considered as one of the causes of anterior uveitis in a pseudophakic patient.
Cataract Extraction/*adverse effects ; Corneal Edema/*etiology/*pathology ; Humans ; Lens, Crystalline/*pathology/surgery ; Male ; Middle Aged ; Postoperative Complications/pathology/surgery ; Pseudophakia/pathology ; Reoperation ; Severity of Illness Index ; Uveitis, Anterior/*etiology/*pathology

PURPOSE: Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) METHODS: EIU was induced in female Lewis rats by single footpad injections of 200 microgram of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients. RESULTS: Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region. CONCLUSIONS: TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.
Animals ; Disease Progression ; Enzyme Inhibitors/*therapeutic use ; Female ; GTP-Binding Proteins/*antagonists & inhibitors/*metabolism ; Lipopolysaccharides ; Rats ; Rats, Inbred Lew ; Transglutaminases/*antagonists & inhibitors/*metabolism ; Uveitis/chemically induced/*enzymology/pathology

We report a case of recurrent occlusion of laser iridotomy (LI) sites after a Visian ICL (Implantable contact lens version 4, Staar Surgical AG, Nidau, Switzerland) implantation. A 45-year-old woman had bilateral ICL implantation after placement of two peripheral LI sites in each eye to prevent pupillary block. At one month after the operation, severe narrowing or occlusion of four LI sites occurred. After this, although she received four additional LIs at postoperative months 1, 6, 9 and 10 in both eyes, the narrowing or occlusion recurred. Mild chronic anterior chamber inflammation was observed intermittently throughout the follow-up period. We performed clear lens extraction in both eyes (at postoperative month 11 in the left eye and month 26 in the right eye) due to recurrent occlusion of the LI sites and excess trabecular meshwork pigment deposition presumably caused by the four repeated LIs. Recurrent obstruction of LI sites can occur after ICL implantation. These problems were unresolvable despite four repeated laser iridotomies. The risks associated with anterior uveitis must be considered when planning an ICL implantation.
Female ; Humans ; Iridectomy/*methods ; Iris/*surgery ; *Laser Therapy ; Lasers, Solid-State ; Lens Implantation, Intraocular/*adverse effects ; Middle Aged ; *Phakic Intraocular Lenses ; Pigment Epithelium of Eye/pathology ; *Postoperative Complications ; Recurrence ; Reoperation ; Trabecular Meshwork/pathology ; Uveitis, Anterior/etiology

Adolescent ; Child ; Humans ; Male ; Nephritis, Interstitial ; pathology ; Uveitis ; pathology