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Masumi Takeda

Publications and source records attributed to Masumi Takeda.

5 recordsLinked to original sources
PubMed2005

Vascular damage in a mouse model of diabetic retinopathy: relation to neuronal and glial changes.

PURPOSE: Lack of information about the development of diabetic retinopathy in mice has greatly hindered the use of genetic mouse models for the study of disease mechanisms and the development of therapeutic strategies. The objective of this study was to characterize the occurrence and pathologic progression of diabetic retinopathy in C57Bl/6J mice. METHODS: Diabetes was induced with five consecutive injections of streptozotocin (STZ). The retinas were collected at different time points (2 weeks to 22 months) after the induction of diabetes and examined by using molecular, histologic, and immunohistochemical techniques and morphometric analysis. RESULTS: There was transient induction of cell apoptosis and caspase-3 activation in retinal neurons of C57Bl/6 mice within days of diabetes induction. Glial fibrillary acidic protein (GFAP), a marker of glial activation, likewise was transiently upregulated, seemingly in astrocytes but not in Müller cells. These abnormalities quickly returned to normal; ultimately, no detectable loss of retinal ganglion cells (RGCs) was noted by any of three independent methods (number of cells in ganglion cell layer of retinal cross-sections, retrograde labeling of retinal ganglion cells with fluorescent dye, or TUNEL staining) after up to a 1-year duration of diabetes. Despite this apparent lack of evidence for progressive damage in neurons and glial cells, diabetic mice developed vascular disease characteristic of the early stage of diabetic retinopathy beginning at 6 months after the onset of disease. The vascular damage-formation of acellular capillaries and pericyte ghosts-continued to increase through the 18 months examined. CONCLUSIONS: Diabetic C57Bl/6J mice develop capillary lesion that are characteristic of the early stages of diabetic retinopathy in patients. The data suggest that diabetes-induced degeneration of retinal capillaries can develop independent of neuronal loss or chronic GFAP upregulation in glial cells.

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PubMed2003

Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin.

With recent progress in neuroscience and stem-cell research, neural transplantation has emerged as a promising therapy for treating CNS diseases. The success of transplantation has been limited, however, by the restricted ability of neural implants to survive and establish neuronal connections with the host. Little is known about the mechanisms responsible for this failure. Neural implantation triggers reactive gliosis, a process accompanied by upregulation of intermediate filaments in astrocytes and formation of astroglial scar tissue. Here we show that the retinas of adult mice deficient in glial fibrillary acidic protein and vimentin, and consequently lacking intermediate filaments in reactive astrocytes and Müller cells, provide a permissive environment for grafted neurons to migrate and extend neurites. The transplanted cells integrated robustly into the host retina with distinct neuronal identity and appropriate neuronal projections. Our results indicate an essential role for reactive astroglial cells in preventing neural graft integration after transplantation.

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PubMed2002

Inhibitory effect of bucillamine on laser-induced choroidal neovascularization in rats.

PURPOSE: We investigated the inhibitory effects of bucillamine on formation of laser-induced choroidal neovascularization (CNV) in a rat model. METHODS: Bucillamine administration (approximately 150 mg/kg/day) was started 1 week before photocoagulation and continued to the end of the study. Control groups received drinking water. Two weeks after photocoagulation, choroidal neovascularization development was evaluated using simultaneous fluorescein and indocyanine green angiography, and the maximal thickness of the lesions was measured histologically. RESULTS: The incidence of CNV formation was 99.5 +/- 0.2% [mean +/- standard deviation (SD)] in control rats and 64.3 +/- 15.1% with bucillamine (P < 0.01). Histological study showed that the thickness of the CNV lesions was 23.4 +/- 6.5 microm (mean +/- SD) in the bucillamine-treated rats, which was significantly decreased compared to that in controls (60.8 +/- 9.2 microm) (P < 0.01). CONCLUSIONS: Our results suggest that bucillamine may inhibit the development of laser-induced CNV in rats.

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PubMed2002

Extracellular signal-regulated kinase activation predominantly in Müller cells of retina with endotoxin-induced uveitis.

PURPOSE: To evaluate the consequences of mitogen-activated protein kinase (MAPK)-mediated signaling in retinas with endotoxin-induced uveitis (EIU). METHODS: EIU was induced with footpad inoculation of lipopolysaccharide (LPS). To identify the expression and activity of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, Western blot analysis and immunohistochemistry (IHC) were performed using antibodies against these kinases and phosphorylated forms. To evaluate the ERK mRNA expression level, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed. To identify cell species that express phosphorylated (p)-ERK, simultaneous demonstration of p-ERK and glial fibrillary acidic protein (GFAP) was performed with combined IHC and in situ hybridization. Dexamethasone (Dex) was used to reduce the LPS-induced inflammatory stimulus, and changes in p-ERK expression were evaluated by Western blot analysis after treatment. RESULTS: Only p-ERK among the phosphorylated MAPKs increased after LPS stimulation, according to Western blot analysis. p-ERK increased after LPS injection, whereas both the Western blot and RT-PCR studies showed no apparent changes in ERK-1 and -2 expression. IHC revealed that strong p-ERK-positive staining initially appeared in the Müller cell bodies. Thereafter p-ERK immunostaining was also observed transiently in the radial processes of the Müller cells. The double-labeling study revealed that almost all Müller cells were positive for GFAP and p-ERK. Dex treatment substantially reduced expression of p-ERK, beginning 12 hours after treatment. CONCLUSIONS: The present study suggests that LPS stimulation activates ERK in Müller cells, whereas the total amount of ERK is unchanged. Because the LPS-induced p-ERK level was reduced by Dex treatment, its expression seems to be associated with ocular inflammatory stimulus. Because the inflammatory stimulus elicited in EIU upregulated ERK activity in Müller cells, activated Müller cells may play a crucial role in protecting retinal cells from such inflammation.

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