Chemogenomic analysis of neuronal differentiation with pathway changes in PC12 cells.

The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database creates networks from interrelations between molecular biology and underlying chemical elements. This allows for analysis of biologic networks, genomic information, and higher-order functional information at a system level. Through high throughput experiments and system biology analysis, we investigated the genes and pathways associated with NGF induced neuronal differentiation. We performed microarray experiments and used the KEGG database, system biology analysis, and annotation of pathway functions to study NGF-induced differentiation in PC12 cells. We identified 2020 NGF-induced genes with altered expressions over time. Cross-matching with the KEGG database revealed 830 genes; among which, 395 altered genes were found to have a 2-fold increase in gene expression over a two-hour period. We then identified 191 associated biologic pathways in the KEGG database; the top 15 pathways showed correlation with neural differentiation. These included the neurotrophin pathways, mitogen-activated protein kinase (MAPK) pathways, genes associated with axonal guidance and the Wnt pathways. The activation of these pathways synchronized with nerve growth factor (NGF)-induced differentiation in PC12 cells. In summary, we have established a model system that allows one to systematically characterize the functional pathway changes in a group of neuronal population after an external stimulus.

Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult.

BACKGROUND: Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood. RESULTS: A decrease in paw withdrawal latency (PWL) after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1) and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (proDYN) gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK) in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK) activity after reinflammation. CONCLUSIONS: Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.

photodynamic therapy for Taiwanese patients with pathologic myopia: a 2-year follow-up.

PURPOSE: To examine the efficacy of photodynamic therapy with verteporfin (VPDT) for treatment of subfoveal choroidal neovascularization (CNV) in patients with pathologic myopia. METHODS: In a prospective study, adult patients (18 years of age or older) with new onset subfoveal CNV were treated in two tertiary centers with the standard protocol of VPDT. Snellen best-corrected visual acuity was measured at baseline and at 1 month, 3 months, 6 months, 12 months, 15 months, 18 months, and 24 months after VPDT. Stratified analyses for single and multiple treatments and different age groups were performed by paired t-tests, and the results were compared with baseline findings. RESULTS: Thirty-three patients with single VPDT and 13 patients with multiple treatments were enrolled for analysis. Significant improvement in measurement of visual acuity was found after 24 months of follow-up for the group with single therapy. For patients receiving multiple treatments, an improving trend was not as clear. In prognosis analysis by age groups in the single-treatment group, the younger group had better mean visual acuity at the end of the 24-month study period than the older group. Improvement was much more evident in the younger group, although it was not statistically significant at every follow-up time point. CONCLUSION: In patients with response to single VPDT, visual acuity significantly improved over a 2-year period. In patients receiving multiple treatments, improvement was not as distinctive, suggesting alternative treatment options might be relevant for this subgroup.

Optic neuropathy and sixth cranial nerve palsy caused by compression from a dolichoectatic basilar artery.

A 53-year-old man with progressive visual loss in the right eye and diplopia manifested dysfunction of the right optic nerve and the right sixth cranial nerve. MRI revealed a markedly enlarged and tortuous basilar artery, its proximal portion compressing the right sixth cranial nerve at the exit from the pons and its distal portion elevating and compressing the right optic nerve. This is the first report of optic neuropathy and sixth cranial nerve palsy caused by a dolichoectatic basilar artery.

Application of transpupillary thermotherapy in a patient with asteroid hyalosis and premacular hemorrhage.

A 70-year-old woman with long-term poor vision was found to have unilateral massive premacular hemorrhage and asteroid hyalosis. Transpupillary thermotherapy (TTT) was applied sequentially to the vitreous in four separate spots, covering the area of the asteroid hyalosis and hemorrhage. Outcome measures included visual acuity, biomicroscopic appearance, ultrasonography, and fluorescein angiography. Significant resolution of the hemorrhage was observed 3 months after TTT, with visual acuity improvement from counting fingers at 25 cm to 20/60. There were no complications noted during the procedure or during follow-up. The long-term safety measures and visual prognosis following TTT for resolution of the vitreous impurities remain to be evaluated, but the procedure may be effective for treating premacular hemorrhage and asteroid hyalosis.

HLA-B27-associated uveitis with a chorioretinitis manifestation.

A 29-year-old man who had been treated for acute anterior uveitis in a local medical office and observed for 1 month presented complaining of distorted vision in his left eye for 1 week. On ophthalmic examination, the anterior segment was relatively quiet with few cells. A posterior segment examination revealed cystoid macular edema and multiple splinter retinal hemorrhages. Results of all laboratory and imaging studies were negative, except for a positive HLA-B27 haplotype. Fluorescein angiography revealed massive leakage in the mid and late phase, consistent with chorioretinitis. Periocular corticosteroid injections and oral prednisolone were administered. The patient responded to the treatment well with subsequent resolution of chorioretinitis 2 months later. Although rare, chorioretinitis can occur in the setting of uveitis associated with HLA-B27 and seems to respond well to corticosteroid treatment.