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

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• 作者：Ben Mead¹ ; ² ; ^* ; ^{BXM813@bham.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Lisa J. Hill¹ ; ^* ; Richard J. Blanch¹ ; Kelly Ward¹ ; Ann Logan¹ ; Martin Berry¹ ; Wendy Leadbeater¹ ; Ben A. Scheven²
• 关键词：dental pulp stem cells ; glaucoma ; stem cell transplantation ; mesenchymal stromal cells ; neuroprotection ; retinal ganglion cells
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：18
• 期：4
• 页码：487-496
• 全文大小：1213 K

文摘

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.