The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains unclear. RGCs are a group of central nervous system (CNS) neurons whose soma are in the inner retina. The axons of RGCs form the optic nerve and converge at the optic chiasma; from there, they project to the visual cortex via the lateral geniculate nucleus (LGN). In recent years, there has been increasing interest in the dysfunction and death of CNS and retinal neurons caused by transneuronal degeneration of RGCs, and the view that glaucoma is a widespread neurodegenerative disease involving CNS damage appears more and more frequently in the literature. In this review, we summarize the current knowledge of LGN and visual cortex neuron damage in glaucoma and possible mechanisms behind the damage. This review presents an updated and expanded view of neuronal damage in glaucoma, and reveals new and potential targets for neuroprotection and treatment.

L-3-n-butylphthalide(NBP), a compound found in Apium graveolens Linn seed extracts, has a therapeutic effect on acute ischemic stroke. The pathological inflammatory pathways and consequent brain edema in intracerebral hemorrhage (ICH) share some similar characteristics with ischemic stroke. We hypothesized that NBP has anti-inflammatory and therapeutic effects on rats with ICH. ICH was induced by an infusion of bacterial collagenase type IV into the unilateral striatum of anesthetized rats. The therapeutic effect of NBP was measured by assessing neurological function, brain water content, blood-brain barrier permeability, and expression of tumor necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) around the hematoma 48 hours after surgery. Magnetic resonance imaging was performed 4 and 48 hours after ICH induction, and ICH-induced injured area volumes were measured using T2-weighted images. The NBP treatment group performed better in the neurological function test than the vehicle group. Moreover, in comparison with the vehicle group, NBP group showed a lower expanded hematoma volume, brain water content, blood-brain barrier permeability, and TNF-α/ MMP-9 expression level. Our results indicate that NBP attenuates inflammation and brain edema in rat ICH model. Therefore, our findings also provide a potential therapeutic strategy for the treatment of ICH with NBP.

Retinoblastoma (RB) is a common neoplasm that is exhibited in individuals globally. Increasing evidence demonstrated that cyclin-dependent kinase regulatory subunit 1B (CKS1B) may be involved in the pathogenesis of various tumor types, including multiple myeloma and breast cancer. In the present study, the hypothesis that CKS1B down-regulation would effectively inhibit the proliferation, invasion and angiogenesis of RB cells through the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was examined. Initial investigation of the expression profile of CKS1B in RB and adjacent retina tissues was performed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. A total of three RB cell lines, SO-RB50, Y79 and HXO-RB44, were examined for selection of the cell line with the highest expression of CKS1B, and human normal retinal vascular endothelial cells (ACBRI-181) were also evaluated. CKS1B short hairpin RNA (shRNA) sequences (shRNA CKS1B-1, shRNA CKS1B-2 and shRNA CKS1B-3) and negative control shRNA sequences were constructed and transfected into cells at the third generation to evaluate the role of shCKS1B and the MEK/ERK signaling pathway in RB. Furthermore, the effect of shCKS1B on cell proliferation, migration, invasion, apoptosis and angiogenesis was investigated. CKS1B was determined to be highly expressed in RB tissue, compared with adjacent retina tissue. SO-RB50 and HXO-RB44 cells treated with shRNA CKS1B-1 and shRNA CKS1B-2 were selected for the present experiments. Activation of the MEK/ERK signaling pathway increases the expression of MEK, ERK, B-cell lymphoma 2, proliferating cell nuclear antigen, cyclin D1, vascular endothelia growth factor and basic fibroblast growth factor, enhances cell proliferation, migration, invasion and lumen formation, and decreases apoptosis. Following silencing CKS1B, the aforementioned conditions were reversed. The key observations of the present study demonstrated that shCKS1B can inhibit the proliferation, invasion and angiogenesis of RB cells by suppressing the MEK/ERK signaling pathway. Thus, CKS1B represents a potential research target in the development of therapeutics for RB.

Although stimulation of aldosterone secretion is one of the functions of angiotensin II, the gene expression and biological significance of the angiotensin II receptor subtypes, AT1 and AT2, in the human adrenal have not been characterized. We therefore investigated the transcription levels of the receptor subtype genes and their roles in regulation of steroid secretion by human adrenals. The expression of AT1 and AT2 receptor mRNA was assessed by reverse transcription-polymerase chain reaction followed by Southern blot analysis in normal adrenocortical tissues (n = 6) and a series of adrenal tumour tissues: aldosterone-producing adrenocortical adenoma (n=6), Cushing's syndrome (n = 6) and pheochromocytoma (n = 6). The role of the two receptor subtypes in steroid secretion in vitro was examined by incubating the tissue with angiotensin II(1 microM) with or without the selective AT1 antagonist CV-11974 (1 microM). Both AT1 and AT2 receptor mRNA transcripts were demonstrated in all of the human adrenal tissues tested. Angiotensin II-induced aldosterone secretion was suppressed 50% upon the addition of CV-11974. The selective AT2 agonist CGP-42112 increased aldosterone secretion by 55% over the control, which was not suppressed by CV-11974. Angiotensin II and CGP-42112 did not affect cortisol secretion. These results suggest that both AT2 and AT1 receptors may be involved in the regulation of aldosterone secretion and tumorigenesis of the human adrenals.

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