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Mark O M Tso

Publications and source records attributed to Mark O M Tso.

14 recordsLinked to original sources
PubMed2005

Activation of microglia and chemokines in light-induced retinal degeneration.

PURPOSE: Microglial cells, which are activated and recruited by chemokines, have been shown to play crucial roles in neuronal degenerations of the central nervous system (CNS). This study investigated the activation and migration of retinal microglial cells and expression of chemokines in retinas in light-induced photoreceptor degeneration in mice. METHODS: Ninety-five Balb/cJ mice were kept in cyclic light for 1 week followed by dark adaptation for 48 h prior to light exposure of 3 h at 3.5 Klux. Animals were enthuanized at various times after light exposure. Terminal deoxynucleotidyl transferase-mediated dUTP nick end label (TUNEL) assay, rat-anti-mouse CD11b and 5D4 antibodies, isolectin-B4, and a chemokine-specific gene array were used to detect DNA fragmentation during retinal degeneration, to label retinal microglial cells, and to determine the expression of retinal chemokines and chemokine receptors, respectively. Reverse-transcriptase coupled polymerase chain reactions (RT-PCRs) were conducted on selected chemokine mRNAs to confirm the gene array findings. RESULTS: After intense light exposure, TUNEL-positive cells were noted in the outer nuclear layer (ONL) of the retina at 3 h, and their presence were noticeably increased at 1 day but declined at 3 days and 7 days after light exposure. In contrast, CD11b- or isolectin-B4-positive cells were seen in the ONL as early as 6 h and their presence increased significantly at 1 day and 3 days after light exposure. These cells displayed a round or ovoid morphology at 6 h and 1 day but assumed a more ameboid configuration at 3 days. By 7 day, the number of the microglial cells declined in the ONL and they became ramified, and were present mostly in the subretinal space. 5D4-positive cells with large cell bodies were only noted at 3 day and 7 day but not earlier. With chemokine-specific gene array analysis, we identified four chemokines and two chemokine receptors showing significant increases in their gene expressions. Among them, monocyte chemoattractant protein-3 (MCP-3), showed a remarkable 4.4 fold increase in its gene expression. RT-PCR confirmed a marked increase of MCP-3 expression in retinas at 3 h to 1 day, and a return to normal at 3 days following light injury. CONCLUSIONS: Retinal chemokines such as MCP-3 and their receptors are involved in the activation and migration of retinal microglia in light-induced retinal degeneration, which in turn modulate the apoptotic loss of photoreceptor cells in the outer retina.

Animals↗
PubMed2005

Minocycline inhibits LPS-induced retinal microglia activation.

Retinal neurodegenerative disease involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retinal injury following an inflammatory stimulus. Cytokines released by activated microglia regulate the influx of inflammatory cells to the damaged area. Thus, a therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Minocycline, a semisynthetic tetracycline derivative, is known to protect rodent brain from ischemia and to inhibit microglial activation. In this study, we activated retinal microglia in culture with lipopolysaccharide (LPS) and attempted to determine whether minocycline could reduce the production of cytokines from activated microglia at both gene and protein levels. Changes in inflammatory cytokines, TNF-alpha and IL-1beta, were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in the presence or absence of LPS. We also measured the levels of nitric oxide (NO) by the nitrate reductase method under similar conditions. LPS treatment induced a significant upregulation of the mRNA and release of TNF-alpha, IL-1beta, and NO from retinal microglia. Minocycline inhibited these releases. Thus, minocycline might exert its antiinflammatory effect on microglia by inhibiting the expression and release of TNF-alpha, IL-1beta, and NO.

Animals↗
PubMed2005

Preface.

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Biomedical Research↗
PubMed2005

Identification of sequential events and factors associated with microglial activation, migration, and cytotoxicity in retinal degeneration in rd mice.

PURPOSE: To elucidate the role of activated microglia in the photoreceptor apoptosis of rd mice by identifying sequential events and factors associated with microglial activation, migration, and cytotoxicity during retinal degeneration. METHODS: Photoreceptor apoptosis in rd mice at postnatal days (P)8, 10, 12, 14, 16, and 18 was detected by terminal dUTP transferase nick end labeling (TUNEL). Retinal microglia were identified by CD11b antibody. Expression of chemokine mRNA, including monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T-cell expressed and secreted (RANTES), interferon-gamma-inducible 10-kDa protein (IP-10), and fractalkine in the retina were examined by reverse transcription-polymerase chain reaction (RT-PCR) assay. Production of tumor necrosis factor (TNF)-alpha in the dystrophic retina was studied by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry analysis. Microglial expression of TNF-alpha was determined by double immunolabeling. RESULTS: Whereas photoreceptor apoptosis in the rd mice started at P10 and reached a peak at P16, activation and migration of microglial cells were observed at P10 and peaked at P14. The expression of MCP-1, MCP-3, MIP-1alpha, MIP-1beta, and RANTES transcripts were noted at P8 and reached a peak at P12. Production of TNF-alpha was noted in the outer nuclear layer (ONL) of the rd mice at P8 and reached a peak at P12. At the peak of microglial activity, TNF-alpha was predominantly expressed in the activated microglial cells in the ONL. CONCLUSIONS: Activation of microglia, as well as expression of their signaling molecules (chemokines) and microglia-derived toxic factor (TNF-alpha), coincides with or precedes the occurrence of photoreceptor apoptosis, suggesting activated microglia play a major role in retinal degeneration in rd mice. The chemokines MCP-1, MCP-3, MIP-1alpha, MIP-1beta, and RANTES are involved in activation and recruitment of the microglia to the degenerating photoreceptor cell layer. TNF-alpha, produced by the activated microglia, may accentuate the photoreceptor cell death.

Animals↗
PubMed2004

Effects of intravitreal indocyanine green injection in rabbits.

PURPOSE: To report the clinical, electrophysiologic, and histologic findings of different concentrations of indocyanine green (ICG) injected into the vitreous cavity of rabbit eyes. METHODS: Forty-two rabbits underwent intravitreal injection of 0.1 mL of ICG in three different concentrations: 0.5 mg/mL (250 mOsm), 5 mg/mL (270 mOsm), and 25 mg/mL (170 mOsm). Fellow eyes were injected with 0.1 mL of balanced salt solution. Biomicroscopy, ophthalmoscopy, electroretinography, fluorescein angiography, and histologic evaluation were performed. RESULTS: Eyes injected with 0.5 mg/mL of ICG showed b-wave latency delay on the first day after injection. Eyes injected with 5 mg/mL of ICG showed b-wave latency delay and decreased b-wave amplitude on the first and seventh days after injection; delayed a-wave latency on the first day after injection was also observed. Eyes injected with 25 mg/mL of ICG showed b- and a-wave amplitude and latency abnormalities during the entire follow-up. Direct correlation of increasing retinal edema proportional to the progressively increasing ICG concentrations was shown on histologic evaluation. CONCLUSION: Intravitreal ICG injection in rabbit eyes may impair retinal function and morphology proportional to the progressively increasing ICG dosages.

Animals↗
PubMed2004

Neuroprotection of photoreceptors by minocycline in light-induced retinal degeneration.

PURPOSE: Microglial cells have been found to play pivotal roles in various neuronal degenerative diseases such as Parkinson's and Alzheimer's diseases. Minocycline, a microglial inhibitor, has recently been shown to be neuroprotective in various models of cerebral ischemia and degenerative diseases of the brain. This study was conducted to evaluate the neuroprotective effect of minocycline and the role of microglia in light-induced retinal degeneration. METHODS: BALB/cJ mice were exposed to intense green light for 3 hours and observed during 1, 3, or 7 days of dark recovery. The animals received intraperitoneal injections of minocycline or vehicle 1 day before exposure to light for 2, 4, or 8 days, depending on the periods of survival. Morphologic, morphometric, immunohistochemical, and electrophysiological studies were performed to evaluate the efficacy of minocycline in the amelioration of light-induced retinal degeneration and the possible involvement of microglial cells. RESULTS: Minocycline treatment provided marked amelioration in the loss of photoreceptors in light-induced retinal degeneration, as evidenced by morphologic, morphometric, and electrophysiologic criteria. Morphologically, the minocycline-treated group showed markedly better preservation of the outer retina after exposure to light. Morphometrically, at 7 days after exposure to light, in the minocycline-treated animals, 89.1% of the normal-appearing photoreceptor nuclei remained, but in the retinas of the vehicle-control group only 38.0% of these nuclei remained. This difference was statistically significant (P < 0.001). At 7 days after exposure to light electroretinography (ERG) showed that minocycline significantly preserved the amplitudes of dark-adapted a- and b-wave and light-adapted b-wave, which were all significantly reduced after exposure to light. Concomitant with this protective effect, at 3 days after exposure to light, the CD11b(+) microglial cells in the outer nuclear layer (ONL) and subretinal space in the minocycline-treated group were significantly decreased (by 63.5%) when compared with those in the light-exposed, vehicle-treated control group (P < 0.01). CONCLUSIONS: Minocycline is neuroprotective against light-induced loss of photoreceptors, possibly through the inhibition of retinal microglial activation.

Animals↗
PubMed2003

Characterization of activated retinal microglia following optic axotomy.

Microglia are prominently involved in neural degenerative diseases of the CNS and the retina. In this study, we determined the activation and phagocytotic function of different subtypes of retinal microglial cells at 1 week and 1 month following optic axotomy. Fluorescent DiI crystals were placed at the stumps of the cut optic nerves of Lewis rats to retrolabel retinal ganglion cells. Microglial cells were indirectly labeled as they phagocytosed the dye particles in the dying ganglion cells. OX-42, 5D4, ED1, and OX-6 antibodies were used for immunohistochemical study. The OX-42- and 5D4-positive microglial cells were increased in the inner retinal layers after optic axotomy. The increase of OX-42-positive cells was considerably greater than that of 5D4-positive cells. The 5D4-positive cells were ramified in shape, whereas OX-42-positive cells were ameboid and ovoid. Both 5D4- and OX-42-positive cells phagocytosed dying ganglion cells at 1 week and 1 month after axotomy. Scattered ameboid ED1-positive cells were detected in the normal retina and showed phagocytotic activity at 1 month after optic axotomy. The number of ED1-positive cells in the retina was unchanged after axotomy. In optic axotomy, three types of microglial cells were activated, namely, 5D4-positive ramified cells and OX-42- and ED1-positive ameboid cells. All of them exhibited the phagocytosis of dying ganglion cells. Insofar as the blood-retinal barrier presumably remained intact in optic axotomy, the OX-42- and 5D4-positive cells might derive from resident microglial cells. The ED1-positive cells, presumably recently blood-borne macrophage in the CNS, remained the same number in the axotomized retina.

Amino Acids↗
PubMed2003

Increased nuclear factor-kappa B p65 immunoreactivity following retinal ischemia and reperfusion injury in mice.

Nuclear factor-kappaB (NF-kappaB) is a universal transcription factor and has previously been demonstrated to play an important role in CNS injury. This study investigated the expression of NF-kappaB in the inner layers of the retina in mice after retinal ischemia and reperfusion injury. Retinal ischemia was induced by elevation of intraocular pressure to 120 mmHg for 60 min. To evaluate inner retinal degeneration, the inner retinal thickness was quantified with an image-analysis system. The inner retinal thickness increased in the initial 24 hr after retinal ischemia and was ascribed to tissue edema but was significantly decreased in the ensuing 7 days. Immunohistochemistry using NF-kappaB p65 monoclonal antibody was performed on the retina and was corelated with TUNEL labeling. Six hours after retinal ischemia, nuclear p65 immunoreactivity was increased in the inner nuclear and ganglion cell layers and reached a peak at 24 hr. The increased NF-kappaB p65 immunolabeling was parallel to the TUNEL labeling. Double labeling with p65 and TUNEL showed partial colocalization of p65 and TUNEL labeling in the scattered cells of the inner nuclear and ganglion cell layers. However, several p65-positive cells were TUNEL negative, suggesting that these cells might have survived the injury. The NF-kappaB p65 immunoreactivity was associated with retinal degeneration following retinal ischemia and reperfusion injury.

Animals↗
PubMed2003

Light-induced photoreceptor degeneration may involve the NF kappa B/caspase-1 pathway in vivo.

PURPOSE: To determine the role of nuclear factor-kappaB (NFkappaB) in light-induced photoreceptor degeneration. METHODS: Dark-adapted BALB/cJ mice, 4-8 weeks, were exposed to an intense green light (3.1-3.5 klux) for 1, 3, 6, 9, 12, or 24 h and killed immediately after exposure. The photoreceptor apoptosis was detected by TUNEL. Co-localization of NFkappaB p65 immunoreactivity and TUNEL in photoreceptor cells was detected by double immunolabeling. The protein levels of X-linked inhibitor of apoptosis protein (XIAP), Bcl-xL, caspase-1, and opsin after light exposure were analyzed by Western blot analysis. In addition, the initiation of NFkappaB activation was assessed by measuring the increase in phosphorylated IkappaBalpha (pIkappaBalpha). Immunohistochemical localization of caspase-1 was also performed on the mouse retinas. RESULTS: Co-localization of NFkappaB p65 immunoreactivity with TUNEL was observed in scattered photoreceptor cells after 24 h of light exposure. The amount of pIkappaBalpha was increased after 1 h of light exposure, and in parallel, the amounts of XIAP and Bcl-xL were increased at 1 h. In contrast, caspase-1 did not increase until after 6 h of light exposure. Caspase-1-immunolabeling was observed in scattered photoreceptor cells after 3 h of light exposure but was markedly increased in many more cells at 6 h. CONCLUSIONS: These findings suggest that NFkappaB may play an anti-apoptotic role in the early response to light stress and that photoreceptor apoptosis induced by light stress may be mediated through an NFkappaB/caspase-1 pathway.

Animals↗
PubMed2003

Autologous transplantation of retinal pigment epithelium after mechanical debridement of Bruch's membrane.

PURPOSE: To determine whether transplantation of autologous retinal pigment epithelium (RPE) will prevent atrophy of the choriocapillaris and loss of photoreceptors in an area in which the RPE has been mechanically debrided from Bruch's membrane. METHODS: Abrasive debridement of RPE was performed with a metal cannula after localized retinal bleb detachments in two separate areas of the rabbit retina. The RPE cell suspension aspirated from one of the debridement sites was transplanted to the other. The debridement-only site served as control. The transplant and control sites were evaluated after 30 days by color fundus photography, fluorescein angiography, light microscopy and transmission electron microscopy. RESULTS: Compared with debridement only, debridement plus transplantation of RPE resulted in more complete repopulation of the bare Bruch's membrane surface with relative preservation of choriocapillaris and photoreceptors. CONCLUSION: Autologous transplantation of RPE onto an abrasively debrided Bruch's membrane decreases choriocapillaris atrophy and photoreceptor loss.

Animals↗
PubMed2003

Early glial responses after acute elevated intraocular pressure in rats.

PURPOSE: To study the responses of glial cells to a short-term elevation in intraocular pressure (IOP) in rats. METHODS: Adult Sprague-Dawley albino rats, 45 to 55 days old, were given India ink intracamerally. After 7 days, 200 spots of laser burn over 360 degrees were delivered by an Argon laser (620-637 nm; 200 mW; 200 mm; 0.2 seconds) aimed at the ink deposits in the trabecular meshwork. IOP was recorded and eye tissues at 12 hours and 1, 3, 5, 7, or 14 days after laser were examined by immunohistochemistry with antibodies against glial fibrillary acidic protein (GFAP), vimentin, S-100, ED1, and OX42. To evaluate neuronal loss, the number of cells in the retinal ganglion cell layer (RGCL) was counted on flat preparations of retinas at various times after elevation of IOP. RESULTS: Significant elevation of IOP from 1 to 7 days and loss of cells in the RGCL from 3 days onward were noted after trabecular laser photocoagulation. In the inner retina, there was a gradual and sustained increase in GFAP and S-100 immunoreactivity, but only a transient increase in vimentin immunoreactivity. No remarkable changes in GFAP, vimentin, and S-100 immunoreactivity were noted at the optic nerve head (ONH). ED1- and OX42-labeled cells were noted in the choroidal plexus, the parapapillary region of the optic nerve, and the ONH from 3 days onward, whereas expression in the retina was unremarkable. CONCLUSIONS: There is differential expression of glial cell markers in the retina and the ONH, with early loss of cells in the RGCL in response to the elevation of IOP. Macroglia such as astrocytes and Müller cells may be involved in the pathophysiology of retinal ganglion cell death or retinal repair, and activated microglial/phagocytic cells may play an important role in modulating the changes in the ONH that occur with the elevation of IOP.

Acute Disease↗
PubMed2002

NF-kappaB activation in light-induced retinal degeneration in a mouse model.

PURPOSE: To investigate the modulation of nuclear factor (NF)-kappaB in light-induced photoreceptor degeneration in a mouse model. METHODS: Mice were exposed to intense green light. Light-induced activation of NF-kappaB and its nuclear localization were studied by immunohistochemistry. The NF-kappaB DNA-binding activity in the retinas after exposure to light was measured by electrophoretic mobility shift assay (EMSA). Nuclear transactivation of NF-kappaB in the photoreceptor cells was determined by quantitative real-time (qRT)-PCR. The amount of NF-kappaB p65 in the photoreceptor cells after exposure to light was assessed by Western blot analysis. To obtain more photoreceptor-specific information, microdissected photoreceptor cells were used in some studies. RESULTS: By an immunohistochemical method, the perinuclear region of the photoreceptor cells was heavily labeled with an antibody to activated NF-kappaB after a 1-hour exposure to light. Nuclear localization of NF-kappaB in the photoreceptor nucleus was seen at 12 hours. In the experiments involving 3 hours of exposure to light followed by recovery in the dark, nuclear localization of NF-kappaB was also noted after 12 hours' recovery in the dark. During continuous exposure to light, the NF-kappaB DNA-binding activity gradually increased and reached its maximum at 12 hours. There was an increase of NF-kappaB p65 protein at 3 hours. The mRNA levels of IkappaBalpha were upregulated after 6 hours' exposure to light. CONCLUSIONS: Intense light activated NF-kappaB in the photoreceptor cells in vivo, increased the NF-kappaB DNA-binding activity, and increased the expression of mRNA of IkappaBalpha, a target gene of NF-kappaB.

Animals↗
PubMedDate not supplied

Frosted branch angiitis secondary to macular choroidal neovascularization in a chinese woman.

BACKGROUND: This is perhaps the first report of frosted branch angiitis secondary to choroidal neovascularization (CNV) from China. We describe a case of frosted branch angiitis associated with macular CNV. CASE: A 19-year-old Chinese woman complained of metamorphopsia and blurred vision in the right eye on August 27, 2002. OBSERVATIONS: Fluorescein angiography demonstrated CNV in the macula. Five months later, focal and atrophic choroidal scars were observed in the macular area. She complained of blurred vision again on April 14, 2003. Iridocyclitis and frosted branch angiitis were found in both fundi. Following treatment with systemic acycloguanosine and corticosteroids for 4 months, the fundi recovered almost completely. CONCLUSIONS: A case of frosted branch angiitis secondary to macular choroidal neovascularization is reported in a Chinese woman. The relation between frosted branch angiitis and CNV remains to be further explored.

Adult↗