Noriaki Kido

Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death

PURPOSE To determine if brain-derived neurotrophic factor (BDNF) has a neuroprotective effect against N-methyl-D-aspartate (NMDA)-induced cell death in retina. METHODS NMDA was injected into the vitreous of rat eyes. NMDA-induced neuronal death was measured by morphometric analyses on cell counts of ganglion cell layer cells and thickness of retinal layers. Also, we conducted additional experiment using retrograde labeling with a fluorescent tracer (Fluoro-Gold) for exact counting of retinal ganglion cells (RGCs). In addition, intravitreal glutamate levels were measured with the use of a high-performance liquid chromatography (HPLC) system. RESULTS Morphometric analysis of retinal damage in NMDA-injected eyes showed that BDNF could protect inner retinal cells from glutamate receptor-mediated neuronal death. Also, counts of RGCs labeled with a fluorescent tracer showed that BDNF could protect RGCs from glutamate receptor-mediated neuronal death. Furthermore, measurements of intravitreal glutamate levels indicated an increase in this excitatory amino acid in the vitreous after NMDA injection. CONCLUSIONS Exogenous BDNF can protect inner retinal cells (possible RGCs and amacrine cells) from NMDA-induced neuronal death. However, increased intravitreal glutamate levels in response to NMDA-mediated neurotoxicity may augment retinal degeneration.

Neuroprotective effects of interleukin-6 on NMDA-induced rat retinal damage.

This study shows that interleukin-6 (IL-6) combined with soluble interleukin-6 receptors (sIL-6R) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Eyes pretreated with a combined injection of IL-6 and sIL-6R had NMDA administered into the vitreous cavity. Morphometric analysis and retrograde labeling analysis found that pretreatment with either IL-6 or sIL-6R alone did not bring about any neuroprotective effect. However, pretreatment with a combined administration of IL-6 and sIL-6R induced a significant neuroprotective effect against NMDA-induced retinal damage. Apoptotic changes in the retina were assessed by the TUNEL method. The results indicated that pretreatment with IL-6 combined with sIL-6R prevents NMDA-induced apoptosis. Western blotting studies demonstrated upregulation of gp130 expression in the NMDA-injected retina. Present studies suggest that IL-6 combined with sIL-6R provides a neuroprotective effect on NMDA-induced retinal damage.

Dual effects of interleukin-1β on N-methyl-d-aspartate-induced retinal neuronal death in rat eyes

In this study we determine if interleukin-1beta (IL-1beta) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Sprague-Dawley rats were anesthetized with inhalation of halothane, after which a single injection of 5 microl of IL-1beta (0.1 to 10 ng/eye) (and/or IL-1 receptor antagonist (IL-1ra)) for experimental eyes was administered. Two days later (or simultaneously), NMDA (20 nmol) was injected into the vitreous space. One week later, each eye was enucleated and transverse sections were subjected to morphometric analysis. Enzyme-linked immunosorbent assay (ELISA) was conducted for the determination of IL-1beta levels in retina. Immunohistochemical and immunoblot studies were also performed. In eyes that received an intravitreal injection of IL-1beta (0.1 to 10 ng/eye), significant thinning of the inner plexiform layer (IPL) was observed (P<0.05). Immunohistochemical and ELISA studies demonstrated upregulated expression of IL-1beta in retinas that had undergone NMDA injection. Treatment with 10 ng of IL-1ra induced a protective effect against NMDA-induced retinal damage. Pretreatment with IL-1beta induced a significant protective effect on NMDA-induced retinal damage. Our studies suggest that IL-1beta induces neuronal cell death directly, as shown by the protective effects of IL-1ra, but has a protective effect on NMDA-induced retinal damage indirectly after an incubation time of at least 2 days.

Secondary glaucoma associated with crystalline lens subluxation

Purpose: To elucidate the clinical characteristics of secondary glaucoma associated with subluxation of the crystalline lens. Setting: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, and Department of Ophthalmology, Tenri Hospital, Nara, Japan. Methods: This retrospective study comprised 14 eyes of 13 patients with uncontrolled intraocular pressure (IOP) and lens subluxation. The subluxated lens was extracted through surgery. Results: Angle closure caused by the subluxated lens was complicated in 3 eyes. In the remaining 11 eyes, uncontrolled IOP elevation was found despite the presence of deep anterior chambers and wide open angles. A mean of 14.1 months ± 13.7 (SD) after cataract surgery, IOP was well controlled (lower than 21 mm Hg) in all 14 eyes. Mean IOP was 15.4 ± 2.2 mm Hg at the final examination. Complications included transient vitreous hemorrhage in 5 eyes, choroidal detachment in 2 eyes, and retinal tears in 1 eye. Conclusion: Lens extraction surgery was effective in controlling IOP in eyes with secondary glaucoma associated with lens subluxation.

Upregulated expression of N-syndecan, a transmembrane heparan sulfate proteoglycan, in differentiated neural stem cells

Adult rat hippocampus-derived neural stem cells are incorporated into neural tissues, and differentiate to neuronal and glial cells. However, the cell surface protein molecules are, to date, undefined. RT-PCR, immunoblotting and immunocytochemistry showed the increased expression of N-syndecan, a transmembrane heparan sulfate proteoglycan, in the neural stem cells after the differentiation induced by retinoic acid. Our data indicate that N-syndecan may be involved in the differentiation of neural stem cells.

Transient intraocular pressure elevation after trabeculotomy and its occurrence with phacoemulsification and intraocular lens implantation.

PURPOSE To elucidate the characterization of intraocular pressure (IOP) spike after trabeculotomy, and after the combined procedure of phacoemulsification and aspiration (PEA) and intraocular lens (IOL) implantation. METHODS Included in this study were 39 patients (53 eyes) with primary open-angle glaucoma with IOPs uncontrolled even with anti-glaucoma medication. We conducted a retrospective study for the following two groups: Patients who underwent trabeculotomy alone (25 eyes) and patients undergoing trabeculotomy combined with PEA and implantation of an IOL (28 eyes). RESULTS In 7 (28%) of the 25 eyes after trabeculotomy alone and 7 (25%) of the 28 eyes after the combined procedure, transient IOP elevation was found postoperatively. The incidence of hyphema-related IOP spike was significantly higher in eyes after trabeculotomy alone (16%) than after the combined procedure (0%). After removal of the blood present in the anterior chamber in eyes with hyphema-related IOP spikes, the IOP levels were well controlled. CONCLUSIONS Hyphema-related IOP spike is one of the common complications in eyes after trabeculotomy alone, and the combined procedure decreases the incidence of this complication. It is thought that removal of prolonged massive hyphema is effective as treatment for hyphema-related IOP spike.