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1.
Neuroscience ; 311: 56-66, 2015 Dec 17.
Article in English | MEDLINE | ID: mdl-26432953

ABSTRACT

When retinal ganglion cells undergo apoptosis after optic nerve (ON) injury, microglial cells proliferate and promptly clear the degenerated debris in the ipsilateral retina. However, microglial changes in the contralateral retina have not been fully elucidated. This study characterized the long-term bilateral retinal microglial responses after unilateral ON transection. We analyzed the time course of proliferation and morphology changes of microglial cells, between 3 days and 12 weeks post ON transection, of undisturbed and reactive microglia in bilateral retinas of adult Fischer rats with unilateral ON transection. Microglia in retinas without ON transection were distributed homogeneously and possessed a highly ramified morphology, as judged by immunohistochemistry for ionized calcium-binding adapter molecule 1 (Iba1). After ON transection, microglia density in the ipsilateral retina increased gradually from 3 days to 2 weeks, and decreased from 3 weeks to 12 weeks, along with dramatic inverted alteration of process branch points of microglia in the ganglion cell layer (GCL). Transformation of ramified microglia into ameboid-like macrophages with few branching processes was observed in the ipsilateral retina from 1 week to 3 weeks. Though an increase in microglial density was weak in the contralateral retina and could only be statistically detected in the central retina, the morphological alteration over time was obvious and similar to that of the ipsilateral retina. In the inner plexiform layer (IPL), cell density and morphological changes of microglia in both the ipsilateral and contralateral retina were not prominent. These findings indicates that, though proliferation of microglial cells is weak in the contralateral retina after unilateral ON transection, conspicuous alterations in microglial morphology occur bilaterally. These suggest that using the contralateral retina as a control in studies of retinal degeneration should be considered with caution.


Subject(s)
Functional Laterality/physiology , Microglia/physiology , Optic Nerve Injuries/physiopathology , Retina/physiopathology , Animals , Calcium-Binding Proteins/metabolism , Cell Count , Cell Proliferation/physiology , Disease Models, Animal , Female , Immunohistochemistry , Macrophages/pathology , Macrophages/physiology , Microfilament Proteins/metabolism , Microglia/pathology , Optic Nerve Injuries/pathology , Rats, Inbred F344 , Retina/pathology
2.
Neuroscience ; 153(1): 214-25, 2008 Apr 22.
Article in English | MEDLINE | ID: mdl-18358617

ABSTRACT

Intraocular pressure (IOP) elevation has often been used as an experimental model to study mechanisms underlying retinal ganglion cell (RGC) death associated with ocular ischemic injury and glaucoma. The aim of the present study, using both in vitro and in vivo approaches, was to investigate the role of phosphatidylinositol 3-kinase (PI3K)/akt pathway in RGC viability in normal rats and rats following transient IOP elevation. For in vivo studies, pathway inhibitors were administered intravitreally on days 3, 9, and 15 post-2-h IOP elevation at 110 mm Hg. Toward the end of the 3-week examination period, the fluorescent dye Fluorogold was used to retrogradely label surviving RGCs. In order to examine the role of macrophages that were recruited into the eye following the pathway inhibition, clodronate liposomes were used to deplete phagocytic cells in the eye. PI3K/akt pathway activity and location in the retina were examined using Western blot and immunohistochemistry, respectively. Here we showed that PI3K/akt inhibitors 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and KY12420 at low concentrations (2 microM or 20 microM) did not influence RGC survival but caused RGC loss at high concentration (200 muM) in retinal explants derived from intact rats. In contrast, both LY294002 and KY12420 at 20 microM led to RGC loss in retinal explants derived from IOP-elevated eyes. A detrimental action of phagocytic cells on RGC survival was also seen in these retinas. In vivo results confirmed the detrimental actions of PI3K/akt inhibition and macrophages on RGC survival in IOP-elevated, but not intact eyes even with high concentration of LY294002. Low level of PI3K/akt activity was detected in the ganglion cell layer (GCL) in intact retina. Acute IOP elevation activated PI3K/akt pathway in the inner nuclear layer and GCL including RGCs. This study thus demonstrates that PI3K/akt pathway mediates RGC survival after IOP elevation but not under normal condition.


Subject(s)
Ocular Hypertension/enzymology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Retinal Ganglion Cells/enzymology , Animals , Cell Survival/physiology , Chemotaxis, Leukocyte/drug effects , Chemotaxis, Leukocyte/physiology , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Ocular Hypertension/pathology , Ocular Hypertension/physiopathology , Phosphoinositide-3 Kinase Inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Retinal Ganglion Cells/pathology , Signal Transduction/physiology , Stilbamidines
3.
Rev Soc Bras Med Trop ; 30(1): 57-60, 1997.
Article in English | MEDLINE | ID: mdl-8993107

ABSTRACT

Schistosomiasis japonica has long been endemic in the People's Republic of China. In the 1950s, the number of the infected persons was estimated at 10 million; infected snail habitats were estimated at more than 14 billion square metres and infected cattle at 1.2 million. After schistosomiasis control measures were carried out, it was a great success. According to the survey of 1989, infected persons were estimated at 0.95 million; infected snails at 3.47 billion and infected cattle at about 0.1 million. These results compared with those of the 1950s show big reductions in prevalence rates 90.5%, 75.2% and 91.6%, respectively. At present, the disease is a threat in the marshland and lake regions and the high mountainous regions. To maintain the success achieved in effective control and to bring the yet endemic marshland and lake regions and mountainous areas under control are hard and long-term tasks confronting the People's Republic of China.


Subject(s)
Disease Outbreaks , Schistosomiasis/epidemiology , Topography, Medical , China/epidemiology , Humans , Schistosomiasis/prevention & control
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