Dendrimer mediated targeted delivery of sinomenine for the treatment of acute neuroinflammation in traumatic brain injury.

Traumatic brain injury (TBI) is a significant medical problem with limited treatment options and is one of the main causes of life-long disability. Neuroinflammation orchestrated by activated microglia/macrophages at the site of injury plays a critical role in the onset of many pathological events following TBI, leading to blood brain barrier (BBB) dysfunction, neuronal damage and long term neuronal and behavioral deficits. Current treatment involves intravenous administration of anti-inflammatory drugs which have limited clinical outcomes only when dosed within the early time window after injury.

Pathologic study of early manifestations of polypoidal choroidal vasculopathy and pathogenesis of choroidal neo-vascularization.

Purpose: To describe the histopathologic features of an early case of presumably bilateral polypoidal choroidal vasculopathy (PCV) in two eyes obtained at autopsy from a patient with no prior ocular therapy.

Observations: The choroid of both eyes at the macular and peripapillary regions was greatly thickened with dilated, thin walled choroidal venules intertwining with arteriosclerotic arterioles in the Sattler's layer of the choroidal vasculature. At the temporal and nasal equatorial regions of both eyes many of these congested venular channels abruptly disappeared and were replaced by loose connective tissue with loss of the normal choroidal stromal tissue and uveal melanocytes.

Ocular Histopathology and Immunohistochemical Analysis in the Oldest Known Individual with Autosomal Dominant Vitreoretinochoroidopathy.

Purpose: To assess the immunohistochemical and histopathological changes in a subject with Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC).

Design: Case study.

Participant: Ninety two year-old Caucasian male with ADVIRC.

A review of the immunologic findings observed in retinitis pigmentosa.

Most patients suffering from retinitis pigmentosa (RP) inherit the disorder; however, the immune-pathologic features associated with this disease have yet to be extensively studied. Six reports correlate antiretinal immune activity with vision deterioration in RP patients. Some of these patients have sporadic RP that occurs in excess of expected gene segregation during inheritance.

Proteolytic Degradation and Inflammation Play Critical Roles in Polypoidal Choroidal Vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a common subtype of wet age-related macular degeneration in Asian populations, whereas choroidal neovascularization is the typical subtype in Western populations. The cause of PCV is unknown. By comparing the phenotype of a PCV mouse model expressing protease high temperature requirement factor A1 (HTRA1) in retinal pigment epithelium with transgenic mice expressing the inactive HTRA1, we showed that HTRA1-mediated degradation of elastin in choroidal vessels is critical for the development of PCV, which exhibited destructive extracellular matrix remodeling and vascular smooth muscle cell loss.

Role of endoplasmic reticulum stress in the loss of retinal ganglion cells in diabetic retinopathy.

Endoplasmic reticulum stress is closely involved in the early stage of diabetic retinopathy. In the present study, a streptozotocin-induced diabetic animal model was given an intraperitoneal injection of tauroursodeoxycholic acid. Results from immunofluorescent co-localization experiments showed that both caspase-12 protein and c-Jun N-terminal kinase 1 phosphorylation levels significantly in-creased, which was associated with retinal ganglion cell death in diabetic retinas.

The international council of ophthalmology: vision for ophthalmic education in an interdependent world.

Purpose: To describe the emerging strategic global perspective of the International Council of Ophthalmology (ICO) efforts in ophthalmic education.

Design: A global perspective describing how the development of sophisticated educational tools in tandem with information technology can revolutionize ophthalmic education worldwide.

Methods: Review of ICO educational tools, resources, and programs that are available to ophthalmic educators across the globe.

Toxic effect of methamphetamine on the retina of CD1 mice.

Purpose: To investigate whether systemic administration of methamphetamine (METH) induces retinal damage in CD1 mice.

Materials And Methods: Eighteen male CD1 mice were randomly assigned to three groups, six mice per group: Group 1 receiving a single dose of 40 mg/kg METH, Group 2 receiving four doses of 10 mg/kg METH, and Group 3 (control) receiving 40 mg/kg 0.9% NaCl solution.

Autophagy, exosomes and drusen formation in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of loss of vision in developed countries. AMD is characterized by a progressive degeneration of the macula of the retina, usually bilateral, leading to a severe decrease in central vision. An early sign of AMD is the appearance of drusen, which are extracellular deposits that accumulate on Bruch's membrane below the retinal pigment epithelium (RPE).

[Endoplasmic reticulum stress proteins are activated in rd retinal degeneration].

Objective: To investigate the expression of endoplasmic reticulum (ER) stress proteins in photoreceptor apoptosis in rd mouse (Pde6bRd1/Rd1).

Methods: Photoreceptor apoptosis in rd mouse was detected by terminal dUTP transferase nick end labeling (TUNEL). The protein expression of ER stress sensors including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2alpha (eIF2alpha) and phospho-pancreatic ER kinase (PERK) was examined by immunofluorescence and Western Blot analysis.

Differentiation of rabbit bone marrow mesenchymal stem cells into corneal epithelial cells in vivo and ex vivo.

Purpose: To examine whether bone marrow mesenchymal stem cells (MSCs) could be differentiated into corneal epithelial cells in vivo and ex vivo.

Methods: In vivo, BrdU labeled rabbit MSCs (Rb-MSCs) were suspended in the fibrin gels and transplanted onto the surface of the damaged rabbit corneas. Histology and molecular phenotype were studied on postoperative day 28.

Autophagy and exosomes in the aged retinal pigment epithelium: possible relevance to drusen formation and age-related macular degeneration.

Age-related macular degeneration (AMD) is a major cause of loss of central vision in the elderly. The formation of drusen, an extracellular, amorphous deposit of material on Bruch's membrane in the macula of the retina, occurs early in the course of the disease. Although some of the molecular components of drusen are known, there is no understanding of the cell biology that leads to the formation of drusen.

Baicalein reduces inflammatory process in a rodent model of diabetic retinopathy.

Purpose: This study was designed to elucidate the role of inflammatory process in diabetic retinopathy and to investigate the effect of baicalein treatment on diabetic rat.

Methods: Retinal microglial cells were identified with CD11b antibody, and retinal Müller cells were identified with glial fibrillary acidic protein (GFAP). The gene expression of interleukin (IL)-18, tumor necrosis factor (TNF)-alpha, and IL-1beta was examined by quantitative real-time PCR.

[Activation of endoplasmic reticulum stress proteins in light-induced retinal degeneration].

Objective: To investigate the expression of endoplasmic reticulum stress proteins in photoreceptor apoptosis in light-induced retinal degeneration.

Methods: Exposure to excessive levels of light induced photoreceptor apoptosis and had been previously used as a model for the study of retinal degeneration. Photoreceptor apoptosis was detected by terminal dUTP transferase nick end labeling (TUNEL).

Early retinal vascular abnormalities in African-American cocaine users.

Purpose: To investigate whether cocaine use is associated with early retinal vascular abnormalities.

Design: Population-based cross-sectional study.

Settings: Inner-city neighborhoods in Baltimore, Maryland.

Activation of nuclear factor-kappaB during retinal degeneration in rd mice.

Purpose: Transcription factors of the nuclear factor-kappa beta (NF-kappaB) family have been demonstrated to play an important role in the regulation of gene expression in the chronic neurodegenerative disorders. The aims of the current study were to investigate the alteration of NF-kappaB activity during retinal degeneration in rd mice and further explore its role in photoreceptor apoptosis.

Methods: Activation of NF-kappaB and its nuclear translocation in the retina of rd mice at postnatal days (P) 8, 10, 12, 14, 16, 18, and 28 were studied by immunohistochemical analysis using NF-kappaB P65 antibody.

Microglial activation in human diabetic retinopathy.

Objective: To investigate microglial activation in human diabetic retinopathy.

Methods: Paraffin sections from 21 eyes of 13 patients with diabetic background, preproliferative, or proliferative retinopathies and 10 normal eyes of 9 individuals were studied with immunolabeling of microglia with antibodies against HLA-DR antigen, CD45, or CD68.

Results: In the healthy human eyes, ramified microglial cells were scattered in the inner retinal layers.

[Pathological study of retinal excitotoxicity following subretinal injection of NMDA].

Objective: To study neuronal excitotoxicity induced by subretinal injection of glutamate analogues.

Methods: We injected 30 mmol/L N-methyl-D-aspartate (NMDA) in 10 microl of DMEM/F12 into subretinal blebs in 24 one-month-old rabbits that were killed 0.5, 1, 2 or 7 days after injection.

A possible mechanism of microglia-photoreceptor crosstalk.

Purpose: The goal of this study was to explore the relationship between photoreceptor apoptosis and retinal microglial activation.

Methods: A murine photoreceptor cell line (661W cells) was exposed to LPS-treated microglial cell conditioned medium (MGCM), and cell viability was assessed by terminal dUTP transferase nick end labeling (TUNEL) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, microglia were exposed to culture media from light-damaged 661W photoreceptor cells (PRCM), and microglial activation was assessed morphologically by phase contrast microscopy.

Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse.

Purpose: Endoplasmic reticulum (ER) stress has been implicated in a wide variety of neurodegenerative disorders of the central nervous system (CNS). This study was designed to elucidate the role of ER stress in photoreceptor apoptosis in the rd1 mouse.

Methods: Photoreceptor apoptosis in the rd1 mouse was detected by terminal dUTP transferase nick-end labeling (TUNEL).

Endoplasmic reticulum stress is activated in light-induced retinal degeneration.

Exposure to excessive levels of light induces photoreceptor apoptosis and has previously been used as a model for the study of retinal degeneration. During the light exposure, intracellular calcium levels increase, and reactive oxygen species (ROS) are generated, which have been shown to cause endoplasmic reticulum (ER) stress. In the present study, we investigated the role of ER stress in light-induced photoreceptor apoptosis.

Sinomenine inhibits activation of rat retinal microglia induced by advanced glycation end products.

Diabetic retinopathy involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retina injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area.

Role of NF-kappaB and MAPKs in light-induced photoreceptor apoptosis.

Purpose: To elucidate the role of nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPKs) in light-induced apoptosis of photoreceptors in culture and to explore the potential inhibitory effect of minocycline and sulforaphane on apoptosis.

Methods: Apoptosis of 661W cells was induced by exposure to light and was detected by terminal dUTP transferase nick end labeling (TUNEL). The mRNA expression and protein production of 10 chemokines and noxious factors were examined by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).