Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshio; Takahashi, Masayo

doi:10.1073/pnas.0402129101

Cited by 414 publications

(388 citation statements)

References 39 publications

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“…In addition to progenitor cells, Müller glia are also reported to have the potential to generate new neurons in response to acute retinal injury in the adult retina (35,36). Therefore, it is of interest to label and trace the fate of Müller glia in living animals by using Müller glia-specific promoters.…”

Section: Discussionmentioning

confidence: 99%

Controlled expression of transgenes introduced by in vivo electroporation

Matsuda

Cepko

2007

Proc. Natl. Acad. Sci. U.S.A.

612

601

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In vivo electroporation is a powerful technique for the introduction of genes into organisms. Temporal and spatial regulation of expression of introduced genes, or of RNAi, would further enhance the utility of this method. Here we demonstrate conditional regulation of gene expression from electroporated plasmids in the postnatal rat retina and the embryonic mouse brain. For temporal regulation, Cre/loxP-mediated inducible expression vectors were used in combination with a vector expressing a conditionally active form of Cre recombinase, which is activated by 4-hydroxytamoxifen. Onset of gene expression was regulated by the timing of 4-hydroxytamoxifen administration. For spatial regulation, transgenes were expressed by using promoters specific for rod photoreceptors, bipolar cells, amacrine cells, Mü ller glia or progenitor cells. Combinations of these constructs will facilitate a variety of experiments, including cell-typespecific gene misexpression, conditional RNAi, and fate mapping of progenitor and precursor cells.G ain-of-function and loss-of-function studies using transgenic animals have greatly advanced our understanding of the molecular and cellular mechanisms of development and disease. In particular, conditional gene activation and inactivation have been powerful methods for studies of gene function and for the labeling and manipulation of specific cell populations in vivo (1, 2). Site-specific recombination systems (Cre/loxP and Flp/FRT) are widely used to control gene expression in transgenic mice. By crossing two transgenic lines, one expressing Cre (or Flp) under tissue-specific and/or inducible control and the other carrying two loxP (or FRT) sites, DNA recombination can lead to inducible gene expression or loss of gene expression in restricted tissues at specific times (3). Although such strategies are very useful, they are time-consuming and cannot be applied to species that are difficult to manipulate genetically.In vivo electroporation is a convenient technique for the introduction of genes into a variety of animals, including mouse, rat, and chick (4, 5). We previously reported that plasmid DNAs can be easily delivered to developing mouse/rat retinas by in vivo electroporation (6). The plasmid DNAs, electroporated from the scleral side of the postnatal day 0 (P0) retina, are preferentially introduced into retinal progenitor/precursor cells, which give rise to four different cell types; rod photoreceptors in the outer nuclear layer (ONL), bipolar and amacrine cells in the inner nuclear layer (INL), and Müller glial cells, which extend radial processes spanning the entire thickness of the retina [see supporting information (SI) Fig. 7]. The efficiency of electroporation into the developing postnatal retina is quite good, and transgene expression persists at least for a few months. Moreover, compared with other gene transfer methods, such as viral vectors, in vivo electroporation has several advantages. First, various types of DNA constructs, including RNAi vectors, are readily introduced to th...

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Section: Discussionmentioning

confidence: 99%

Controlled expression of transgenes introduced by in vivo electroporation

Matsuda

Cepko

2007

Proc. Natl. Acad. Sci. U.S.A.

612

601

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“…Some of these cells may become spatially restricted to the peripheral retina from which they can be cultured as neurospheres (17). In addition, Müller glia in the avian and mouse retina can proliferate and retain multipotency in situ in response to injury (41,42), and a small fraction of murine cells can exhibit such properties after a culture period (31).…”

Section: Discussionmentioning

confidence: 99%

Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property

Jadhav

Cho

Cepko

2006

Proc. Natl. Acad. Sci. U.S.A.

158

147

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Signaling through the Notch pathway regulates multiple aspects of development. The vertebrate retina allows an investigation of the basis for these various effects, because the major cell types of the retina arise from a common progenitor that expresses Notch1 . The Notch pathway was constitutively activated in distinct populations of retinal cells during development. Prolonged Notch activity in progenitor cells maintained cells in the progenitor state without perturbing temporal identity, promoting early progenitor characteristics early in development and late progenitor characteristics later in development. Eventually, constitutive Notch activation led these cells to acquire characteristics of glial and stem cells. In contrast, reactivating the Notch pathway in newly postmitotic retinal cells promoted mature glial cell formation in a subset of cells. These data suggest that prolonged Notch activity does not disrupt the normal progression of progenitor temporal states, and that down-regulating or overcoming Notch activity is required for proper formation of both neuronal and glial cell fates.

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“…Recent experimental evidence suggests that a subset of the Muller glia constitute an INL population of progenitor cells in fish and other vertebrates (Bernardos, et al, 2007;Fausett and Goldman, 2006;Fimble, et al, 2007;Reh, 2001 &Ooto, et al, 2004;Yurco and Cameron, 2005). In teleosts including zebrafish, mechanical damage, chemical toxicity, and phototoxicity stimulated an increase in proliferation of cells in the INL and ONL (Fausett and Goldman, 2006;Vihtelic and Hyde, 2000;Vihtelic, et al, 2006;Wu et al, 2001).…”

Section: Stem Cells and Photoreceptor Regenerationmentioning

confidence: 99%

Zebrafish: A model system for the study of eye genetics

Fadool

Dowling

2008

Progress in Retinal and Eye Research

195

172

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Over the last decade, the use of the zebrafish as a genetic model has moved beyond the proof-ofconcept for the analysis of vertebrate embryonic development to demonstrated utility as a mainstream model organism for the understanding of human disease. The initial identification of a variety of zebrafish mutations affecting the eye and retina, and the subsequent cloning of mutated genes have revealed cellular, molecular and physiological processes fundamental to visual system development. With the increasing development of genetic manipulations, sophisticated techniques for phenotypic characterization, behavioral approaches and screening strategies, the identification of novel genes or novel gene functions will have important implications for our understanding of human eye diseases, pathogenesis, and treatment.

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Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

Cited by 414 publications

References 39 publications

Controlled expression of transgenes introduced by in vivo electroporation

Controlled expression of transgenes introduced by in vivo electroporation

Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property

Zebrafish: A model system for the study of eye genetics

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