Retinal microglia exacerbate uveitis by functioning as local antigen-presenting cells.

Autoimmune uveitis is a major cause of blindness in the working-age population of developed countries. Experimental autoimmune uveitis (EAU) depends on activation of interphotoreceptor retinoid-binding protein (IRBP) specific CD4 effector T cells that migrate systemically and infiltrate into the retina. Following systemic induction of retinal antigen-specific T cells, the development of EAU can be broken down into three phases: early phase when inflammatory cells begin to infiltrate the retina, amplification phase, and peak phase.

CD47 Deficiency Ameliorates Ocular Autoimmune Inflammation.

Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. The CD47 is a ubiquitously expressed transmembrane protein which plays multiple roles in fundamental cellular functions including phagocytosis, proliferation, and adhesion. Signal regulatory protein alpha (SIRPα), one of the CD47 ligands, is predominantly expressed in myeloid lineage cells such as dendritic cells (DCs) or macrophages, and CD47-SIRPα signaling pathway is implicated in the development of autoimmune diseases.

Retinal microglia initiate neuroinflammation in ocular autoimmunity.

Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis.

Mouse model of ocular hypertension with retinal ganglion cell degeneration.

Objectives: Ocular hypertension is a primary risk factor for glaucoma and results in retinal ganglion cell (RGC) degeneration. Current animal models of glaucoma lack severe RGC cell death as seen in glaucoma, making assessment of physiological mediators of cell death difficult. We developed a modified mouse model of ocular hypertension whereby long-lasting elevation of intraocular pressure (IOP) is achieved, resulting in significant reproducible damage to RGCs.

Microglia inhibit photoreceptor cell death and regulate immune cell infiltration in response to retinal detachment.

Retinal detachment (RD) is a sight-threatening complication common in many highly prevalent retinal disorders. RD rapidly leads to photoreceptor cell death beginning within 12 h following detachment. In patients with sustained RD, progressive visual decline due to photoreceptor cell death is common, leading to significant and permanent loss of vision.

The Complement System Is Critical in Maintaining Retinal Integrity during Aging.

The complement system is a key component of innate immunity comprised of soluble components that form a proteolytic cascade leading to the generation of effector molecules involved in cellular clearance. This system is highly activated not only under general inflammatory conditions such as infections, collagen diseases, nephritis, and liver diseases, but also in focal ocular diseases. However, little is known about the role of the complement system in retinal homeostasis during aging.

Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation.

Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors.

Background: To examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors.

Methods: Thirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L.

Clinical Profile of Anti-Myelin Oligodendrocyte Glycoprotein Antibody Seropositive Cases of Optic Neuritis.

We have studied the clinical picture of anti-aquaporin antibody (AQP4-Ab)- and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-positive optic neuritis. However, optic neuritis associated with MOG-Abs has not been elucidated using new methods such as cell-based assay. Hence, we conducted a comprehensive investigation on its clinical profile.

Differences in the clinical features of two types of Vogt-Koyanagi-Harada disease: serous retinal detachment and optic disc swelling.

Purpose: To elucidate the clinical differences between serous retinal detachment (RD)-type and optic disc (OD) swelling-type Vogt-Koyanagi-Harada (VKH) disease.

Methods: We performed a retrospective review of 96 patients with new-onset, active VKH disease. Patients were classified into serous RD-type or OD swelling-type VKH disease groups by means of optical coherence tomography and fluorescein angiography, and the differences between the 2 groups were analyzed.

Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection.

Purpose: To measure intraocular cytokine levels in patients with exudative age-related macular degeneration and analyze changes in the cytokine profile 2 days after intravitreal bevacizumab injection.

Methods: This prospective case-control study enrolled 37 patients (37 eyes) with age-related macular degeneration including polypoidal choroidal vasculopathy. Twenty-eight age-matched patients (28 eyes) who underwent cataract surgery were used as controls.

Prediction of severe cardiac involvement by fundus lesion in sarcoidosis.

Purpose: We examined the relation between ocular sarcoidosis and severe cardiac sarcoidosis necessitating pacemaker implantation.

Methods: In this retrospective, observational, cross-sectional study, we reviewed the clinical records of 108 patients diagnosed with ocular sarcoidosis based on new diagnostic criteria established in Japan. We examined and compared the relationship between fundus findings of ocular sarcoidosis and severe cardiac sarcoidosis necessitating pacemaker implantation.

Peroxisome proliferator-activated receptor-γ agonist pioglitazone suppresses experimental autoimmune uveitis.

Peroxisome proliferator-activated receptor (PPAR)-γ agonists are clinically used as anti-diabetes agents. Recent research has discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. In the present study, we investigated the anti-inflammatory effects of PPAR-γ agonist, pioglitazone, on murine model of endogenous uveitis.

Effects of soluble CD14 and cytokine levels on diabetic macular edema and visual acuity.

Purpose: The pathogenesis of diabetic retinopathy has been suggested to be associated with ocular inflammation. Macrophages and monocytes that infiltrate the eye are known to express CD14. After shedding from the membrane-bound CD14, soluble CD14 (sCD14) is released, which could potentially activate inflammatory signaling.

Interleukin-10 gene-transfected mature dendritic cells suppress murine experimental autoimmune optic neuritis.

Purpose: We have reported that calcitonin gene-related peptide gene-transfected mature dendritic cells (mDC) suppress murine experimental autoimmune optic neuritis (EAON) and experimental autoimmune encephalitis (EAE) via interleukin-10 (IL-10) production. In our study, we examined whether IL-10-transfected mDC prevent development of EAON and EAE.

Methods: A plasmid expressing mouse IL-10 was constructed and used to transfect C57BL/6 mouse bone marrow-derived mDC by electroporation methods.

Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy.

Purpose: To investigate whether vitreous and aqueous humor concentrations of vascular endothelial growth factor (VEGF) predict postoperative complications after vitrectomy for proliferative diabetic retinopathy (PDR).

Methods: Sixty eyes of 52 patients with PDR who underwent vitrectomy were enrolled. Vitreous and aqueous humor were obtained from eyes with PDR during primary vitrectomy and the levels of VEGF were measured using a commercial flow cytometer.

Suppression of murine experimental autoimmune optic neuritis by mature dendritic cells transfected with calcitonin gene-related Peptide gene.

Purpose: Calcitonin gene-related peptide (CGRP) exhibits prominent anti-inflammatory actions. We examined whether CGRP-transfected dendritic cells (DC) prevent the development of experimental autoimmune optic neuritis (EAON) and experimental autoimmune encephalomyelitis (EAE).

Methods: A human CGRP-expressing plasmid was constructed, and used to transfect C57BL/6 mouse bone marrow-derived matured DC (mDC) by electroporation

Methods: Transfection efficiency was 50% with 80% cell viability.

Immune mediators in vitreous fluids from patients with vitreoretinal B-cell lymphoma.

Purpose: Various immune mediators are hypothesized to have important roles in the pathogenesis of vitreoretinal B-cell lymphoma, although the exact mechanisms remain unclear. We determined the immune mediator profile in the vitreous of eyes with vitreoretinal B-cell lymphoma.

Methods: We studied 28 eyes (23 patients) with vitreoretinal B-cell lymphoma, and 27 eyes (27 patients) undergoing vitrectomy for macular hole and epiretinal membrane served as controls.

Correlation of complement fragment C5a with inflammatory cytokines in the vitreous of patients with proliferative diabetic retinopathy.

Purpose: To determine the vitreous concentration of complement fragment C5a in patients with proliferative diabetic retinopathy (PDR) and the relation between C5a and inflammatory cytokines including vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1).

Methods: Vitreous samples were obtained at the time of vitrectomy from 12 eyes of 11 PDR patients and from 11 eyes of 11 patients without diabetes with macular disease (controls). Vitreous and serum concentrations of human C5a, VEGF, and MCP-1 were quantified using FACS Caliber flow cytometer.

Costimulatory molecule expression on human uveal melanoma cells: functional analysis of CD40 and B7-H1.

Costimulatory molecules play important roles in regulating T cell function in tumor immunity. In this study, we investigated costimulatory molecule expression on human uveal melanoma cells (a primary culture, and OCM-1, OMM-1 and 92-1 cell lines) and assessed the functional roles of selected costimulatory molecules. Uveal melanoma cells were incubated in the presence or absence of IFN-γ and expression of costimulatory molecules on the cells was measured by flow cytometry.

Increases of vitreous monocyte chemotactic protein 1 and interleukin 8 levels in patients with concurrent hypertension and diabetic retinopathy.

Purpose: To investigate whether concurrent hypertension affects vitreous cytokine levels in diabetic retinopathy.

Methods: Vitreous samples from 41 patients with diabetic retinopathy with or without concurrent hypertension, who underwent vitrectomy, were collected. Vitreous cytokine concentrations were simultaneously measured using flow cytometry.

Relation of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy in branch retinal vein occlusion.

Purpose: To investigate the association of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy for patients with macular edema in branch retinal vein occlusion (BRVO).

Design: Retrospective case-control study.

Methods: Seventeen patients with BRVO who underwent vitreous surgery for macular edema and 15 control patients were enrolled from Hachioji Medical Center of Tokyo Medical University.