Molecular Imaging of Retinal Gliosis in Transgenic Mice Induced by Kainic Acid Neurotoxicity

Ho, Gideon; Kumar, Saravana; Min, Xiao Shan; Kng, Yin Ling; Loh, Ming Yang; Gao, Shujun; Zhuo, Lang

doi:10.1167/iovs.08-2133

Cited by 8 publications

(6 citation statements)

References 28 publications

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“…Since then, transgenic models have been engineered in which astrocytes express GFP (Zhuo et al, 1997; Nolte et al, 2001), allowing for the observation of astrogliosis in brain slices with fluorescent microscopy, and real-time in vivo detection of astrogliosis using multi-photon microscopy. This technique has been employed by several groups investigating systems such as retinal gliosis in diabetes (Kumar and Zhuo, 2010), retinal neurotoxicity (Ho et al, 2009) and NMDA-induced astrocyte activation (Serrano et al, 2008). This transgenic model can also facilitate sorting of astrocytes from surrounding brain tissue, allowing mRNA expression profiling in glioma (Katz et al, 2012), as described above.…”

Section: Imaging Astrocytes In Vivomentioning

confidence: 99%

The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

O’Brien¹,

Howarth²,

Sibson³

2013

Front. Cell. Neurosci.

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Brain metastasis is a significant clinical problem, yet the mechanisms governing tumor cell extravasation across the blood-brain barrier (BBB) and CNS colonization are unclear. Astrocytes are increasingly implicated in the pathogenesis of brain metastasis but in vitro work suggests both tumoricidal and tumor-promoting roles for astrocyte-derived molecules. Also, the involvement of astrogliosis in primary brain tumor progression is under much investigation. However, translation of in vitro findings into in vivo and clinical settings has not been realized. Increasingly sophisticated resources, such as transgenic models and imaging technologies aimed at astrocyte-specific markers, will enable better characterization of astrocyte function in CNS tumors. Techniques such as bioluminescence and in vivo fluorescent cell labeling have potential for understanding the real-time responses of astrocytes to tumor burden. Transgenic models targeting signaling pathways involved in the astrocytic response also hold great promise, allowing translation of in vitro mechanistic findings into pre-clinical models. The challenging nature of in vivo CNS work has slowed progress in this area. Nonetheless, there has been a surge of interest in generating pre-clinical models, yielding insights into cell extravasation across the BBB, as well as immune cell recruitment to the parenchyma. While the function of astrocytes in the tumor microenvironment is still unknown, the relationship between astrogliosis and tumor growth is evident. Here, we review the role of astrogliosis in both primary and secondary brain tumors and outline the potential for the use of novel imaging modalities in research and clinical settings. These imaging approaches have the potential to enhance our understanding of the local host response to tumor progression in the brain, as well as providing new, more sensitive diagnostic imaging methods.

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Section: Imaging Astrocytes In Vivomentioning

confidence: 99%

The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

O’Brien¹,

Howarth²,

Sibson³

2013

Front. Cell. Neurosci.

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“…(Bosco et al, 2015) Ho et al, have also used in vivo longitudinal CSLO imaging to document gliotic responses of astrocytes within the ONH after RGC injury. (Ho et al, 2009)…”

Section: Introductionmentioning

confidence: 99%

In vivo imaging methods to assess glaucomatous optic neuropathy

Fortune

2015

Experimental Eye Research

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The goal of this review is to summarize the most common imaging methods currently applied for in vivo assessment of ocular structure in animal models of experimental glaucoma with an emphasis on translational relevance to clinical studies of the human disease. The most common techniques in current use include optical coherence tomography and scanning laser ophthalmoscopy. In reviewing the application of these and other imaging modalities to study glaucomatous optic neuropathy, this article is organized into three major sections: 1) imaging the optic nerve head, 2) imaging the retinal nerve fiber layer and 3) imaging retinal ganglion cell soma and dendrites. The article concludes with a brief section on possible future directions.

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“…In search for an alternative noninvasive imaging method to investigate the ocular consequence in Parkinsonism or other neurological disorders, we developed a molecular retinal imaging system, comprising of a GFAP‐GFP mouse [16], a confocal scanning laser ophthalmoscope, and an image processing algorithm [14,15]. Results from the current study showed that this imaging system can be applied to study retinopathy in a neurotoxicant (2′‐CH 3 ‐MPTP)‐induced mouse PD model.…”

Section: Discussionmentioning

confidence: 99%

“…For imaging hardware, the second version of Heidelberg Retina Angiograph (HRA II) SLO (Heidelberg Engineering, Dossenheim, Germany) was modified for use on mice. Detailed procedures for imaging and signal quantification were described in our recent publication [14]. The quantified signal values were expressed as mean ± SEM, and statistically tested using Student's two‐tailed t ‐test.…”

Section: Methodsmentioning

confidence: 99%

“…Here, we investigate one of the IMSs, 1,3‐bisbenzylimidazolium bromide (DBZIM), for its possible role in attenuating neurotoxicity and gliosis in the retina and the brain induced by a Parkinsonian neurtoxicant, methyl‐4(2′‐methylphenyl)‐1,2,3,6‐tetrahydropyridine (2′‐CH 3 ‐MPTP), which is a free radical generating agent. In this study, we employ a molecular retinal imaging method, which we recently developed in a transgenic mouse model expressing green fluorescent protein (GFP) under the control of glial fibrillary acidic protein (GFAP) promoter [14], to assess the efficacy of DBZIM, since currently no in vitro system with a sufficient complexity is available for accurately assessing a compound's efficacy. The longitudinal imaging results showed DBZIM can effectively suppress the neurotoxicant‐induced retinal gliosis.…”

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confidence: 99%

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Imidazolium Salt (DBZIM) Reduces Gliosis in Mice Treated with Neurotoxicant 2′-CH3-MPTP

Kumar

Zhao

et al. 2010

CNS Neuroscience &Amp; Therapeutics

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We have recently identified a class of imidazolium salts (IMSs) with antioxidative property and can function as scavengers for radical oxygen species (ROS) [18]. Here, we investigate one of the IMSs, 1,3-bisbenzylimidazolium bromide (DBZIM), for its possible role in attenuating neurotoxicity and gliosis in the retina and the brain induced by a Parkinsonian neurtoxicant, methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH(3) -MPTP), which is a free radical generating agent. In this study, we employ a molecular retinal imaging method, which we recently developed in a transgenic mouse model expressing green fluorescent protein (GFP) under the control of glial fibrillary acidic protein (GFAP) promoter [14], to assess the efficacy of DBZIM, since currently no in vitro system with a sufficient complexity is available for accurately assessing a compound's efficacy. The longitudinal imaging results showed DBZIM can effectively suppress the neurotoxicant-induced retinal gliosis. Immunohistochemistry performed on the postmodern mouse brain confirmed that DBZIM also reduced striatal gliosis, and concomitantly attenuated the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). These findings suggest that DBZIM could be a useful small molecular compound for studying neurotoxicity and neuroprotection in the retina and the brain.

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Molecular Imaging of Retinal Gliosis in Transgenic Mice Induced by Kainic Acid Neurotoxicity

Cited by 8 publications

References 28 publications

The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

In vivo imaging methods to assess glaucomatous optic neuropathy

Imidazolium Salt (DBZIM) Reduces Gliosis in Mice Treated with Neurotoxicant 2′-CH3-MPTP

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