April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Direct optic nerve sheath (DONS) transplantation of Schwann cells reduces RGC death after optic nerve injury
Author Affiliations & Notes
  • Li Guo
    UCL Institute of Ophthalmology, London, United Kingdom
  • Benjamin M Davis
    UCL Institute of Ophthalmology, London, United Kingdom
  • Shereen Nizari
    UCL Institute of Ophthalmology, London, United Kingdom
  • Eduardo Maria Normando
    UCL Institute of Ophthalmology, London, United Kingdom
  • Joana Margarida Galvao
    UCL Institute of Ophthalmology, London, United Kingdom
  • Lisa Turner
    UCL Institute of Ophthalmology, London, United Kingdom
  • Jingwei Shi
    China-Japan Union Hospital, Jilin University, Changchun, China
  • Melanie Clements
    Hammersimith Hospital, Imperial College, London, United Kingdom
  • Simona Parrinello
    Hammersimith Hospital, Imperial College, London, United Kingdom
  • M Francesca Cordeiro
    UCL Institute of Ophthalmology, London, United Kingdom
    Western Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships Li Guo, None; Benjamin Davis, None; Shereen Nizari, None; Eduardo Normando, None; Joana Galvao, None; Lisa Turner, None; Jingwei Shi, None; Melanie Clements, None; Simona Parrinello, None; M Francesca Cordeiro, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2439. doi:
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      Li Guo, Benjamin M Davis, Shereen Nizari, Eduardo Maria Normando, Joana Margarida Galvao, Lisa Turner, Jingwei Shi, Melanie Clements, Simona Parrinello, M Francesca Cordeiro, ; Direct optic nerve sheath (DONS) transplantation of Schwann cells reduces RGC death after optic nerve injury. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2439.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Cell-based therapies are increasingly recognized as a potential strategy to treat retinal degenerative disease. Their administration however, is normally indirect and complex. The aims of this study are to develop a new approach to applying Schwann cells (SCs) directly to the optic nerve sheath (SC/DONS) in a glaucoma-related rat model, and to assess therapeutic effects on protection of retinal ganglion cells (RGCs), compared to SC intravitreal administration (SC/IVT).

Methods: Dark Agouti (DA) rats had partial optic nerve transection (pONT) performed in the left eye. SCs were transplanted either directly to ON sheath (SC/DONS) or intravitreally (SC/IVT), with 2.5µl of 2x108 cells/ml and 5 µl of 2.5x108 cells/ml, respectively. Animals that had pONT done without SC treatment served as control. Animals (n = 4-10 per treatment) were sacrificed at 3, 7, 14, 21, and 56 days following pONT, and retinal whole-mounts were dissected and stained with Brn-3a for RGCs. To automatically count RGCs in the entire retina, a novel algorithm count was developed using ImageJ and compared to the manual count. The effects of SCs on targeting primary and/or secondary degeneration were also assessed.

Results: The algorithm count of RGCs in whole retina was significantly correlated to manual count (Pearson’s correlation coefficient = 0.9860, p<0.0001, R2 = 0.9722), with the total number of RGCs being 80,818±4919 and the RGC density 2152±526 cells/mm2 in normal rat retina. Longitudinal profiles of RGC loss in pONT only rats was best fitted to a one phase exponential decal model. Although both SC/DONS and SC/IVT altered the temporal course of pONT-induced RGC degeneration, SC/DONS resulted in delayed but significantly (p<0.01) prolonged duration of RGC protection, compared to SC/IVT treatment.

Conclusions: SC/DONS is a new method of SC administration which appears to have potential in the treatment of optic neuropathies such as glaucoma. The protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic.

Keywords: 721 stem cells • 615 neuroprotection • 531 ganglion cells  
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