Inhibition of vascular adhesion protein-1 enhances the anti-tumor effects of immune checkpoint inhibitors.

Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein-1 (VAP-1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP-1 in TME was investigated in 2 murine colon cancer models and human cancer cells.

Increased Microcirculation on Optic Nerve Head by Laser Speckle Flowgraphy at Early Stage of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder predominantly affecting young men. Characteristic features of an early stage of LHON are peripapillary telangiectatic microangiopathy with optic disc hyperaemia and swelling of the retinal nerve fibre layers. We evaluated the microcirculation of the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) in a 79-year-old man and a 36-year-old woman with LHON.

Inhibition of Vascular Adhesion Protein-1 for Treatment of Graft-Versus-Host Disease in Mice.

Graft-versus-host disease (GVHD) is a potentially lethal complication of hematopoietic stem cell transplantation (HSCT). GVHD comprises acute and chronic forms. To date, several approaches to treat acute GVHD or chronic GVHD have been reported.

Visual prognosis better in eyes with less severe reduction of visual acuity one year after onset of Leber hereditary optic neuropathy caused by the 11,778 mutation.

Background: Patients with Leber hereditary optic neuropathy (LHON) have a progressive decrease of their visual acuity which can deteriorate to <0.1. Some patients can have a partial recovery of their vision in one or both eyes.

Vascular Adhesion Protein-1 Blockade Suppresses Ocular Inflammation After Retinal Laser Photocoagulation in Mice.

Purpose: To investigate the effect of the vascular adhesion protein-1 (VAP-1) inhibitor RTU-1096 on retinal morphologic changes and ocular inflammation after retinal laser photocoagulation in mice.

Methods: C57BL/6JJcl mice were fed a diet containing RTU-1096, a specific inhibitor for VAP-1, or a control diet ad libitum for 7 days. Laser photocoagulation was performed on the peripheral retina of the animals.

Long-Term Protection of Genetically Ablated Rabbit Retinal Degeneration by Sustained Transscleral Unoprostone Delivery.

Purpose: To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation).

Methods: The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry.

Protective effects of sustained transscleral unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats.

It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing.

Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population.

Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study.

Serum vascular adhesion protein-1 correlates with vascular endothelial growth factor in patients with type II diabetes.

Aims: To study serum levels of soluble vascular adhesion protein (sVAP)-1 in type II diabetic patients with retinopathy.

Methods: Serum samples were obtained from 53 consecutive patients, including 14 cases with non-angiogenic ocular diseases, i.e.

Association of Toll-like receptor 4 gene polymorphisms in Japanese subjects with primary open-angle, normal-tension, and exfoliation glaucoma.

Purpose: To determine whether polymorphisms in the Toll-like receptor 4 (TLR4) gene are associated with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and exfoliation glaucoma (XFG) in Japanese individuals.

Design: Genetic association study.

Setting: Multicenter study.

Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy.

Purpose: Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells.

Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization.

Purpose: Vascular adhesion protein (VAP)-1 is an adhesion molecule elucidated as a mediator of the leukocyte recruitment cascade. The purpose of this study was to investigate the role of VAP-1 in ocular inflammatory neovascularization using a mouse laser-induced choroidal neovascularization (CNV) model.

Methods: CNV was induced with 532 nm laser irradiation in C57BL/6 mice, and production of VAP-1 protein in the retinal pigment epithelium (RPE) choroid during CNV formation was examined.

VAP-1-mediated M2 macrophage infiltration underlies IL-1β- but not VEGF-A-induced lymph- and angiogenesis.

Vascular adhesion protein-1 (VAP-1) contributes to inflammatory and angiogenic diseases, including cancer and age-related macular degeneration. It is expressed in blood vessels and contributes to inflammatory leukocyte recruitment. The cytokines IL-1β and vascular endothelial growth factor A (VEGF-A) modulate angiogenesis, lymphangiogenesis, and leukocyte infiltration.

Vascular adhesion protein-1 regulates leukocyte transmigration rate in the retina during diabetes.

Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity and is involved in leukocyte recruitment. Leukocyte adhesion to retinal vessels is a predominant feature of experimentally induced diabetic retinopathy (DR). However, the role of VAP-1 in this process is unknown.

Effect of unoprostone on topographic and blood flow changes in the ischemic optic nerve head of rabbits.

Objective: To determine whether subconjunctival injection of unoprostone isopropyl alters changes in the topography and blood flow of the optic disc induced by endothelin 1 (ET-1) in rabbits.

Methods: From April 1, 2005, to April 28, 2006, we injected ET-1 (20 pmol) intravitreally into rabbits twice per week for 4 weeks. The observation period was 8 weeks.

Docosahexaenoic acid (DHA) has neuroprotective effects against oxidative stress in retinal ganglion cells.

We examined the radical-scavenging activity of docosahexaenoic acid (DHA) and its effects on the neuronal cell death induced by oxidative or hypoxic stress in cultured retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus). The radical-scavenging activity [hydrogen peroxide (H(2)O(2)), superoxide anion (O(2)*(-)), and hydroxyl radical (*OH)] of DHA in RGC-5 cells was measured using the ROS-sensitive probes CM-H(2)DCFDA and APF. DHA concentration-dependently scavenged the intracellular radical productions induced by H(2)O(2) radical, O(2)*(-), and *OH (minimum effective DHA concentrations 0.

Vascular adhesion protein-1 blockade suppresses choroidal neovascularization.

Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule involved in leukocyte recruitment. Leukocytes and, in particular, macrophages play an important role in the development of choroidal neovascularization (CNV), an integral component of age-related macular degeneration (AMD). Previously, we showed a role for VAP-1 in ocular inflammation.

Woman with atypical unilateral Leber's hereditary optic neuropathy with visual improvement.

We describe a patient with Leber's hereditary optic neuropathy (LHON) who had a unilateral involvement and a gradual recovery of vision. A 50-year-old woman was referred to our clinic in December 2004 for the treatment of left optic neuritis. The visual acuity was 0.

Association between open-angle glaucoma and gene polymorphism for heat-shock protein 70-1.

Purpose: Heat-shock proteins (HSPs) or antibodies against them may contribute to glaucomatous optic neuropathy. We investigated the associations of HSP70-1 polymorphisms with open-angle glaucoma (OAG) in a Japanese population.

Methods: In 241 normal Japanese controls and 501 Japanese OAG patients, including 211 with primary open-angle glaucoma (POAG) and 290 with normal-tension glaucoma (NTG), two single-nucleotide polymorphisms, A-110C and G+190C, of HSP70-1 were identified by using an Invader assay and polymerase chain reaction-restriction fragment length polymorphism, respectively.