Biomedical subjects

Tomomitsu Miyoshi

Publications and source records attributed to Tomomitsu Miyoshi.

6 recordsLinked to original sources

PubMed2006

Xylazine promotes axonal regeneration in the crushed optic nerve of adult rats.

Xylazine, an alpha-2 adrenergic agonist, activates the endogenous trophic factors and neuronal survival signaling. Here, we tested the regenerative effect of xylazine on damaged optic nerve axons in adult rats. After optic nerve crush, xylazine was intraperitoneally injected into three groups of rats: a single administration immediately after the crush, intermittent administration, and daily administration. On day 14, the regenerated axons were quantitatively evaluated by anterograde labeling. Everyday administration but neither single nor intermittent administration markedly increased the number of labeled axons beyond the crush site, with upregulation of growth-associated protein-43 in the ganglion cell layer and the regenerated axons. It was concluded that xylazine promotes axonal regeneration in damaged optic nerves of adult rats.

Adrenergic alpha-Agonists↗

PubMed2006

Attempts to restore visual function after optic nerve damage in adult mammals.

Retinal ganglion cells (RGCs) and their axons, i.e., optic nerve (ON) fibers, provide a good experimental model for research on damaged CNS neurons and their functional ecovery. After the ON transection most RGCs undergo retrograde and anterograde degeneration but they can be rescued and regenerated by transplantation of a piece of peripheral nerve (PN). When the nerve graft was bridged to the visual center, regenerating RGC axons can restore the central visual projection. Behavioral recovery of relatively simple visual function has been proved in such PN-grafted rodents. Intravitreal injections of various neurotrophic factors and cytokines to activate intracellular signaling mechanism of RGCs and electrical stimulation to the cut end of ON have promoting effects on their survival and axonal regeneration. Axotomized RGCs in adult cats are also shown to survive and regenerate their axons through the PN graft. Among the cat RGC types, Y cells, which function as visual motion detector, tend to survive and regenerate axons better than others. X cells, which are essential for acute vision, suffer from rapid death after ON transection but they can be rescued by intravitreal application of neurotrophins accompanied with elevation of cAMP. To restore visual function in adult mammals with damaged optic pathway, the comprehensive and integrative strategies of multiple approaches will be needed, taking care of functional diversity of RGC types.

Animals↗

PubMed2005

Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system.

PURPOSE: To investigate the effect of transcorneal electrical stimulation (TES) on the survival of axotomized RGCs and the mechanism underlying the TES-induced neuroprotection in vivo. METHODS: Adult male Wistar rats received TES after optic nerve (ON) transection. Seven days after the ON transection, the density of the surviving RGCs was determined, to evaluate the neuroprotective effect of TES. The levels of the mRNA and protein of insulin-like growth factor (IGF)-1 in the retina after TES were determined by RT-PCR and Northern and Western blot analyses. The localization of IGF-1 protein in the retina was examined by immunohistochemistry. RESULTS: TES after ON transection increased the survival of axotomized RGCs in vivo, and the degree of rescue depended on the strength of the electric charge. RT-PCR and Northern and Western blot analyses revealed a gradual upregulation of intrinsic IGF-1 in the retina after TES. Immunohistochemical analysis showed that IGF-1 immunoreactivity was localized initially in the endfeet of Muller cells and then diffused into the inner retina. CONCLUSIONS: TES can rescue the axotomized RGCs by increasing the level of IGF-1 production by Muller cells. These findings provide a new therapeutic approach to prevent or delay the degeneration of retinal neurons without the administration of exogenous neurotrophic factors.

Animals↗

PubMed2003

Apoptotic death of beta cells after optic nerve transection in adult cats.

We have revealed previously that the survival rate of beta cells of cat retinal ganglion cells (RGCs) rapidly decreased to 29% on day 7 after optic nerve transection, whereas that of alpha cells slowly decreased to 64% on day 14 (Watanabe et al., 2001). The reason that beta cells die more rapidly than alpha cells was not clear. In the present study, we tested the possibility that the rapid death of beta cells is attributable to apoptosis, as shown for some axotomized RGCs in rats. The following results were obtained. First, the proportion of pyknotic cells in Nissl-stained cat retinas started to increase sharply starting on day 4 and reached a peak on day 6 after optic nerve transection. The time course of occurrence of pyknotic cells corresponded well with that of the rapid death of axotomized beta cells. Secondly, the proportion of pyknotic cells was the highest in the area centralis (AC), in which beta cells are densely distributed. The preferential death of axotomized RGCs in the AC was also confirmed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in cross sections. Thirdly, after the intravitreal injection of caspase 3 inhibitor (z-DEVD-cmk) the survival of axotomized beta cells on day 7 was significantly enhanced, whereas no such survival-promoting effect was obtained in axotomized alpha cells. Taken together, these results suggest that the rapid death of axotomized beta cells is attributable mainly to apoptosis, which is mediated by caspase 3.

Animals↗

PubMed2002

Electrical stimulation enhances the survival of axotomized retinal ganglion cells in vivo.

In view of recent reports on the survival promotion of damaged spiral ganglion cells and motoneurons by electrical stimulation, we hypothesized that an electrical stimulation of the cut optic nerve (ON) may promote the survival of axotomized retinal ganglion cells (RGCs) in vivo. To test this hypothesis, we examined 1 week after ON transection the RGC densities in the retinas with or without electrical stimulation. The densities of surviving RGCs in the retinas with the electrical stimulation increased as compared with those without the electrical stimulation. We concluded that electrical stimulation of the ON enhances the survival of axotomized RGCs in vivo, probably due to electrical activation of their soma.

Animals↗

PubMed2002

Changes in visual response properties of cat retinal ganglion cells within two weeks after axotomy.

After optic nerve transection beta cells of cat retinal ganglion cells (RGCs) suffer from rapid cell death from 3 to 7 days, whereas alpha cells gradual cell death until 14 days. Here we report electrophysiological properties of Y- (morphological alpha) and X- (morphological beta) cells at 5 and 14 days after axotomy in comparison with those of intact Y- and X-cells. Most of the axotomized RGCs revealed characteristic visual response properties that enable us to classify them into Y- or X-cells. Physiological sampling ratio of X-cells sharply decreased from day 5 to 14 after axotomy, corresponding to the previous morphological results. As compared with intact RGCs, axotomized RGCs of both Y- and X-type revealed the following abnormalities: smaller receptive field centers, weaker visual responses and lower spontaneous activities. Intracellular injections of Lucifer yellow into axotomized and intact RGCs at eccentricities 0-6 mm from the area centralis revealed no sign of shrinkage in dendritic field size of either alpha or beta cells on day 5 and day 14 after axotomy, revealing that observed smaller receptive field centers of axotomized RGCs on day 5 were not due to the change of dendritic field sizes. These results suggest that the major events occurring shortly after axotomy are significant loss of synaptic inputs from afferent neurons in the retina and/or changes of membrane properties of axotomized RGCs. These events can also explain lower spontaneous activities and weaker visual responses of axotomized RGCs.

Action Potentials↗