EphA4/ephrinA3 reverse signaling induced Müller cell gliosis and production of pro-inflammatory cytokines in experimental glaucoma.

Previous work showed that ephrinA3/EphA4 forward signaling contributed to retinal ganglion cell (RGC) damage in experimental glaucoma. Since up-regulated patterns of ephrinA3 and EphA4 were observed in Müller cells and RGCs, an EphA4/ephrinA3 reverse signaling may exist in Müller cells of chronic ocular hypertension (COH) retina. We investigated effects of EphA4/ephrinA3 reverse signaling activation on Müller cells in COH retina.

EphA4/ephrinA3 reverse signaling mediated downregulation of glutamate transporter GLAST in Müller cells in an experimental glaucoma model.

Deficiency of glutamate transporter GLAST in Müller cells may be culpable for excessive extracellular glutamate, which involves in retinal ganglion cell (RGC) damage in glaucoma. We elucidated how GLAST was regulated in rat chronic ocular hypertension (COH) model. Western blot and whole-cell patch-clamp recordings showed that GLAST proteins and GLAST-mediated current densities in Müller cells were downregulated at the early stages of COH.

Soluble tumor necrosis factor-alpha-induced hyperexcitability contributes to retinal ganglion cell apoptosis by enhancing Nav1.6 in experimental glaucoma.

Background: Neuroinflammation plays an important role in the pathogenesis of glaucoma. Tumor necrosis factor-alpha (TNF-α) is a major pro-inflammatory cytokine released from activated retinal glial cells in glaucoma. Here, we investigated how TNF-α induces retinal ganglion cell (RGC) hyperexcitability and injury.

Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension.

Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertension (COH), accompanied by activation of Rac1, a member of the Rho family.

Activated ephrinA3/EphA4 forward signaling induces retinal ganglion cell apoptosis in experimental glaucoma.

Previous studies have demonstrated that EphA4 participates in neuronal injury, and there is a strong interaction between ephrinA3 and EphA4. In this study, we showed that in a rat chronic ocular hypertension (COH) experimental glaucoma model, expression of EphA4 and ephrinA3 proteins was increased in retinal cells, including retinal ganglion cells (RGCs) and Müller cells, which may result in ephrinA3/EphA4 forward signaling activation on RGCs, as evidenced by increased p-EphA4/EphA4 ratio. Intravitreal injection of ephrinA3-Fc, an activator of EphA4, mimicked the effect of COH on p-EphA4/EphA4 and induced an increase in TUNEL-positive signals in normal retinas, which was accompanied by dendritic spine retraction and thinner dendrites in RGCs.

K+ Channels of Müller Glial Cells in Retinal Disorders.

Background & Objective: Müller cell is the major type of glial cell in the vertebrate retina. Müller cells express various types of K+ channels, such as inwardly rectifying K+ (Kir) channels, big conductance Ca2+-activated K+ (BKCa) channels, delayed rectifier K+ channels (KDR), and transient A-type K+ channels. These K+ channels play important roles in maintaining physiological functions of Müller cells.

Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis.

Our previous studies have demonstrated that activation of group I metabotropic glutamate receptors downregulated Kir channels in chronic ocular hypertension (COH) rats, thus contributing to Müller cell gliosis, characterized by upregulated expression of glial fibrillary acidic protein (GFAP). In the present study, we explored possible signaling pathways linking Kir channel inhibition and GFAP upregulation. In normal retinas, intravitreal injection of BaCl significantly increased GFAP expression in Müller cells, which was eliminated by co-injecting mitogen-activated protein kinase (MAPK) inhibitor U0126.

Modification and simulation of Rhizomucor miehei lipase: the influence of surficial electrostatic interaction on enantioselectivity.

Surface residues have a significant impact on the enantioselectivity of lipases. But the molecular basis of this has never been explained. In this work, transition state complexes of Rhizomucor miehei lipase (RmL) and (R)- or (S)-n-butyl 2-phenxypropinate were studied using molecular dynamics.

One-stage complete removal of intracardiac leiomyomatosis without cardiac arrest.

We present here a woman with an intracardiac leiomyoma originating from uterine leiomyomatosis. The tumor was completely removed in a one-stage procedure using cardiopulmonary bypass without cardiac arrest. Most one-stage operations were performed with total circulation arrest; however, using of on-pump beating-heart technique when removing the intracardiac mass has seldom been reported in detail.

[Gastrointestinal stromal tumor of small intestine associated with lymph node metastasis: a report of 2 cases with review of literatures].

Objective: To study the clinicopathologic features of gastrointestinal stromal tumor (GIST) of small intestine with lymph node metastasis and evaluate the respond to imatinib mesylate (Glivec) therapy.

Methods: Two cases of GIST of small intestine associated with lymph node metastasis were collected and investigated by light microscopy and immunohistochemistry. Mutation in exon 9, 11 and of c-kit gene were analyzed by polymerase chain reaction and DNA sequencing.

[Inflammatory myofibroblastic tumor of bladder: a clinicopathologic study of five cases].

Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of inflammatory myofibroblastic tumor of the urinary bladder.

Methods: Excisional specimens from 5 cases of vesical inflammatory myofibroblastic tumor were studied by light microscopy and immunohistochemistry (EnVision). The clinical data were also analyzed.

[Sclerosing angiomatoid nodular transformation of spleen].

Objective: To study the clinicopathologic features of sclerosing angiomatoid nodular transformation of spleen and its differential diagnosis.

Methods: The clinicopathologic characteristics and immunophenotype of 4 cases of sclerosing angiomatoid nodular transformation of spleen were studied.

Results: Histologically, all cases were characterized by multiple angiomatoid nodules of various sizes in a fibrosclerotic stroma.