Rescue of retinal ganglion cells from axotomy-induced apoptosis through TRK oncogene transfer. 1998

E Garcia Valenzuela, and S C Sharma
Department of Cell Biology, New York Medical College, Valhalla 10595, USA.

Following axonal injury, central neurons die through programmed cell death. Modification of intracellular mechanisms through specific gene transfer might provide a mechanism for survival. Here we present rescue of rat retinal ganglion cells (RGCs) through gene transfer of TRK oncogenes. Administration of plasmid DNA at the optic axon terminals in the superior colliculus results in retrograde transport to their soma and significant expression of the exogenous DNA. Using this approach for transfection, a TRK oncogene containing plasmid was introduced in RGCs. Three days after plasmid injection, optic nerves were transected. TRK oncogene transfection induced extended survival of the axotomized neurons, lasting over 10 days. Gene delivery to specific cell types is an initial step in the development of therapeutic strategies for regeneration of the damaged nervous system.

UI MeSH Term Description Entries
D008845 Microinjections The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes. Microinjection
D009857 Oncogenes Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene. Transforming Genes,Oncogene,Transforming Gene,Gene, Transforming,Genes, Transforming
D009900 Optic Nerve The 2nd cranial nerve which conveys visual information from the RETINA to the brain. The nerve carries the axons of the RETINAL GANGLION CELLS which sort at the OPTIC CHIASM and continue via the OPTIC TRACTS to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the SUPERIOR COLLICULI and the SUPRACHIASMATIC NUCLEI. Though known as the second cranial nerve, it is considered part of the CENTRAL NERVOUS SYSTEM. Cranial Nerve II,Second Cranial Nerve,Nervus Opticus,Cranial Nerve, Second,Cranial Nerves, Second,Nerve, Optic,Nerve, Second Cranial,Nerves, Optic,Nerves, Second Cranial,Optic Nerves,Second Cranial Nerves
D010957 Plasmids Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS. Episomes,Episome,Plasmid
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012165 Retinal Ganglion Cells Neurons of the innermost layer of the retina, the internal plexiform layer. They are of variable sizes and shapes, and their axons project via the OPTIC NERVE to the brain. A small subset of these cells act as photoreceptors with projections to the SUPRACHIASMATIC NUCLEUS, the center for regulating CIRCADIAN RHYTHM. Cell, Retinal Ganglion,Cells, Retinal Ganglion,Ganglion Cell, Retinal,Ganglion Cells, Retinal,Retinal Ganglion Cell
D013477 Superior Colliculi The anterior pair of the quadrigeminal bodies which coordinate the general behavioral orienting responses to visual stimuli, such as whole-body turning, and reaching. Colliculus, Superior,Optic Lobe, Human,Optic Lobe, Mammalian,Optic Tectum,Anterior Colliculus,Superior Colliculus,Tectum, Optic,Colliculi, Superior,Colliculus, Anterior,Human Optic Lobe,Human Optic Lobes,Mammalian Optic Lobe,Mammalian Optic Lobes,Optic Lobes, Human,Optic Lobes, Mammalian,Optic Tectums,Tectums, Optic
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

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