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Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice

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Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice. / Flachsbarth, Kai; Kruszewski, Katharina; Jung, Gila; Jankowiak, Wanda; Riecken, Kristoffer; Wagenfeld, Lars; Richard, Gisbert; Fehse, Boris; Bartsch, Udo.

In: INVEST OPHTH VIS SCI, Vol. 55, No. 11, 2014, p. 7029-7039.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Flachsbarth, K, Kruszewski, K, Jung, G, Jankowiak, W, Riecken, K, Wagenfeld, L, Richard, G, Fehse, B & Bartsch, U 2014, 'Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice', INVEST OPHTH VIS SCI, vol. 55, no. 11, pp. 7029-7039. https://doi.org/10.1167/iovs.14-15266

APA

Flachsbarth, K., Kruszewski, K., Jung, G., Jankowiak, W., Riecken, K., Wagenfeld, L., Richard, G., Fehse, B., & Bartsch, U. (2014). Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice. INVEST OPHTH VIS SCI, 55(11), 7029-7039. https://doi.org/10.1167/iovs.14-15266

Vancouver

Flachsbarth K, Kruszewski K, Jung G, Jankowiak W, Riecken K, Wagenfeld L et al. Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice. INVEST OPHTH VIS SCI. 2014;55(11):7029-7039. https://doi.org/10.1167/iovs.14-15266

Bibtex

@article{15b35a340545409695e3a5b3b2e51f1e,
title = "Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice",
abstract = "Purpose: To analyze the neuroprotective effect of intravitreally grafted neural stem (NS) cells genetically modified to secrete ciliary neurotrophic factor (CNTF) on intraorbitally lesioned retinal ganglion cells (RGCs) in adult mice. Methods: Adherently cultivated NS cells were genetically modified to express a secretable variant of mouse CNTF together with the fluorescent reporter protein Venus. Clonal CNTF-secreting NS cell lines were established using fluorescence activated cell sorting, and intravitreally grafted into adult mice one day after an intraorbital crush of the optic nerve. Brn-3a-positive RGCs were counted in flat-mounted retinas at different post-lesion intervals to evaluate the neuroprotective effect of the CNTF-secreting NS cells on the axotomized RGCs. Anterograde axonal tracing experiments were performed to analyze the regrowth of the injured RGC axons in CNTF-treated retinas. Results: Intravitreally grafted NS cells preferentially differentiated into astrocytes that survived in the host eyes, stably expressed CNTF, and significantly attenuated the loss of the axotomized RGCs over a period of at least four months, the latest post-lesion time point analyzed. Depending on the post-lesion interval analyzed, the number of RGCs in eyes with grafted CNTF-secreting NS cells was 2.8-fold to 6.4-fold higher than in eyes with grafted control NS cells. The CNTF-secreting NS cells additionally induced long distance regrowth of the lesioned RGC axons. Conclusions: Genetically modified clonal NS cell lines may serve as a useful tool for preclinical studies aimed at evaluating the therapeutic potential of a sustained cell-based intravitreal administration of neuroprotective factors in mouse models of glaucoma.",
author = "Kai Flachsbarth and Katharina Kruszewski and Gila Jung and Wanda Jankowiak and Kristoffer Riecken and Lars Wagenfeld and Gisbert Richard and Boris Fehse and Udo Bartsch",
note = "Copyright {\textcopyright} 2014 by Association for Research in Vision and Ophthalmology.",
year = "2014",
doi = "10.1167/iovs.14-15266",
language = "English",
volume = "55",
pages = "7029--7039",
journal = "INVEST OPHTH VIS SCI",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice

AU - Flachsbarth, Kai

AU - Kruszewski, Katharina

AU - Jung, Gila

AU - Jankowiak, Wanda

AU - Riecken, Kristoffer

AU - Wagenfeld, Lars

AU - Richard, Gisbert

AU - Fehse, Boris

AU - Bartsch, Udo

N1 - Copyright © 2014 by Association for Research in Vision and Ophthalmology.

PY - 2014

Y1 - 2014

N2 - Purpose: To analyze the neuroprotective effect of intravitreally grafted neural stem (NS) cells genetically modified to secrete ciliary neurotrophic factor (CNTF) on intraorbitally lesioned retinal ganglion cells (RGCs) in adult mice. Methods: Adherently cultivated NS cells were genetically modified to express a secretable variant of mouse CNTF together with the fluorescent reporter protein Venus. Clonal CNTF-secreting NS cell lines were established using fluorescence activated cell sorting, and intravitreally grafted into adult mice one day after an intraorbital crush of the optic nerve. Brn-3a-positive RGCs were counted in flat-mounted retinas at different post-lesion intervals to evaluate the neuroprotective effect of the CNTF-secreting NS cells on the axotomized RGCs. Anterograde axonal tracing experiments were performed to analyze the regrowth of the injured RGC axons in CNTF-treated retinas. Results: Intravitreally grafted NS cells preferentially differentiated into astrocytes that survived in the host eyes, stably expressed CNTF, and significantly attenuated the loss of the axotomized RGCs over a period of at least four months, the latest post-lesion time point analyzed. Depending on the post-lesion interval analyzed, the number of RGCs in eyes with grafted CNTF-secreting NS cells was 2.8-fold to 6.4-fold higher than in eyes with grafted control NS cells. The CNTF-secreting NS cells additionally induced long distance regrowth of the lesioned RGC axons. Conclusions: Genetically modified clonal NS cell lines may serve as a useful tool for preclinical studies aimed at evaluating the therapeutic potential of a sustained cell-based intravitreal administration of neuroprotective factors in mouse models of glaucoma.

AB - Purpose: To analyze the neuroprotective effect of intravitreally grafted neural stem (NS) cells genetically modified to secrete ciliary neurotrophic factor (CNTF) on intraorbitally lesioned retinal ganglion cells (RGCs) in adult mice. Methods: Adherently cultivated NS cells were genetically modified to express a secretable variant of mouse CNTF together with the fluorescent reporter protein Venus. Clonal CNTF-secreting NS cell lines were established using fluorescence activated cell sorting, and intravitreally grafted into adult mice one day after an intraorbital crush of the optic nerve. Brn-3a-positive RGCs were counted in flat-mounted retinas at different post-lesion intervals to evaluate the neuroprotective effect of the CNTF-secreting NS cells on the axotomized RGCs. Anterograde axonal tracing experiments were performed to analyze the regrowth of the injured RGC axons in CNTF-treated retinas. Results: Intravitreally grafted NS cells preferentially differentiated into astrocytes that survived in the host eyes, stably expressed CNTF, and significantly attenuated the loss of the axotomized RGCs over a period of at least four months, the latest post-lesion time point analyzed. Depending on the post-lesion interval analyzed, the number of RGCs in eyes with grafted CNTF-secreting NS cells was 2.8-fold to 6.4-fold higher than in eyes with grafted control NS cells. The CNTF-secreting NS cells additionally induced long distance regrowth of the lesioned RGC axons. Conclusions: Genetically modified clonal NS cell lines may serve as a useful tool for preclinical studies aimed at evaluating the therapeutic potential of a sustained cell-based intravitreal administration of neuroprotective factors in mouse models of glaucoma.

U2 - 10.1167/iovs.14-15266

DO - 10.1167/iovs.14-15266

M3 - SCORING: Journal article

C2 - 25270193

VL - 55

SP - 7029

EP - 7039

JO - INVEST OPHTH VIS SCI

JF - INVEST OPHTH VIS SCI

SN - 0146-0404

IS - 11

ER -