Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma

Ben Mead*, Lisa J. Hill, Richard J. Blanch, Kelly Ward, Ann Logan, Martin Berry, Wendy Leadbeater, Ben A. Scheven

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background aims: Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. Methods: Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a+ RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. Results: Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. Discussion: The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma.

Original languageEnglish
Pages (from-to)487-496
Number of pages10
JournalCytotherapy
Volume18
Issue number4
Early online date17 Feb 2016
DOIs
Publication statusPublished - 1 Apr 2016

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Retinal Ganglion Cells
Mesenchymal Stromal Cells
Glaucoma
Dental Pulp
Rodentia
Stem Cells
Nerve Fibers
Cell Count
Bone Marrow
Electroretinography
Retinal Diseases
Optical Coherence Tomography
Stem Cell Transplantation
Blindness
Neuroprotection
Intraocular Pressure
Therapeutics
Hot Temperature
Immunohistochemistry
Neurons

Bibliographical note

© 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • Dental pulp stem cells
  • Glaucoma
  • Mesenchymal stromal cells
  • Neuroprotection
  • Retinal ganglion cells
  • Stem cell transplantation

Cite this

Mead, Ben ; Hill, Lisa J. ; Blanch, Richard J. ; Ward, Kelly ; Logan, Ann ; Berry, Martin ; Leadbeater, Wendy ; Scheven, Ben A. / Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma. In: Cytotherapy. 2016 ; Vol. 18, No. 4. pp. 487-496.
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Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma. / Mead, Ben; Hill, Lisa J.; Blanch, Richard J.; Ward, Kelly; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A.

In: Cytotherapy, Vol. 18, No. 4, 01.04.2016, p. 487-496.

Research output: Contribution to journalArticle

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T1 - Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma

AU - Mead, Ben

AU - Hill, Lisa J.

AU - Blanch, Richard J.

AU - Ward, Kelly

AU - Logan, Ann

AU - Berry, Martin

AU - Leadbeater, Wendy

AU - Scheven, Ben A.

N1 - © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background aims: Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. Methods: Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a+ RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. Results: Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. Discussion: The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma.

AB - Background aims: Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. Methods: Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a+ RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. Results: Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. Discussion: The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma.

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