IJMS Vol 41, No 5, September 2016
Original Article
Neural Stem Cell-based Intraocular Administration of Pigment Epithelium-derived Factor Promotes Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Crush Injury in Rat: An Experimental Study Wei-Min Zhang1, MD; Zhi-Ren Zhang2, MD; Yong-Gang Zhang1, MD; Yan-Sheng Gao1, MD
Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian, China; 2 Department of Medical Administration, Zhumadian Central Hospital, Zhumadian, China 1
Correspondence: Zhi-Ren Zhang, MD; Department of Medical Administration, Zhumadian Central Hospital, Zhumadian, 463000, China Tel: +86 369 2726911 Fax: +86 396 2726209 Email: [email protected] Received: 25 November 2015 Revised: 14 February 2016 Accepted: 06 March 2016
What’s Known • Multiple injections of pigment epithelium-derived factor (PEDF) are prone to cause local damage or infection. Aneural stem cell (NSC)based system could provide sustained delivery of PEDF and reduce local damage or infection.
What’s New • PEDF-NSCs effectively increased RGC survival and improved axon regeneration in the optic nerve compared with weekly injections of PEDF. Our results provide experimental evidence and form the basis for applying cell-based strategies for the local delivery of PEDF into the retina. Application of cell-based delivery may be extended to other disease conditions beyond optic nerve crush injury.
382
Abstract
Background: Pigment epithelium-derived factor (PEDF) is regarded as a multifunctional protein possessing neurotrophic and neuroprotective properties. PEDF has a very short halflife, and it would require multiple injections to maintain a therapeutically relevant level without a delivery system. However, multiple injections are prone to cause local damage or infection. To overcome this, we chose a cell-based system that provided sustained delivery of PEDF and compared the effect of weekly injections of PEDF and neural stem cell (NSC)-based intraocular administration of PEDF on retinal ganglion cell (RGC) survival and axon regeneration after optic nerve injury. Methods: Seventy-two rats were randomly assigned to 3 groups: group with injections of phosphate buffered saline (PBS) (n=24), group with weekly injections of PEDF (n=24), and group with NSC-based administration of PEDF (n=24). Western blot was used to analyze the PEDF protein level 2 weeks after injection. Retinal flat mounts and immunohistochemistry were employed to analyze RGC survival and axon regeneration 2 weeks and 4 weeks after injection. The data were analyzed with one-way ANOVA in SPSS (version 19.0). A P
Original Article
Neural Stem Cell-based Intraocular Administration of Pigment Epithelium-derived Factor Promotes Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Crush Injury in Rat: An Experimental Study Wei-Min Zhang1, MD; Zhi-Ren Zhang2, MD; Yong-Gang Zhang1, MD; Yan-Sheng Gao1, MD
Department of Neurosurgery, Zhumadian Central Hospital, Zhumadian, China; 2 Department of Medical Administration, Zhumadian Central Hospital, Zhumadian, China 1
Correspondence: Zhi-Ren Zhang, MD; Department of Medical Administration, Zhumadian Central Hospital, Zhumadian, 463000, China Tel: +86 369 2726911 Fax: +86 396 2726209 Email: [email protected] Received: 25 November 2015 Revised: 14 February 2016 Accepted: 06 March 2016
What’s Known • Multiple injections of pigment epithelium-derived factor (PEDF) are prone to cause local damage or infection. Aneural stem cell (NSC)based system could provide sustained delivery of PEDF and reduce local damage or infection.
What’s New • PEDF-NSCs effectively increased RGC survival and improved axon regeneration in the optic nerve compared with weekly injections of PEDF. Our results provide experimental evidence and form the basis for applying cell-based strategies for the local delivery of PEDF into the retina. Application of cell-based delivery may be extended to other disease conditions beyond optic nerve crush injury.
382
Abstract
Background: Pigment epithelium-derived factor (PEDF) is regarded as a multifunctional protein possessing neurotrophic and neuroprotective properties. PEDF has a very short halflife, and it would require multiple injections to maintain a therapeutically relevant level without a delivery system. However, multiple injections are prone to cause local damage or infection. To overcome this, we chose a cell-based system that provided sustained delivery of PEDF and compared the effect of weekly injections of PEDF and neural stem cell (NSC)-based intraocular administration of PEDF on retinal ganglion cell (RGC) survival and axon regeneration after optic nerve injury. Methods: Seventy-two rats were randomly assigned to 3 groups: group with injections of phosphate buffered saline (PBS) (n=24), group with weekly injections of PEDF (n=24), and group with NSC-based administration of PEDF (n=24). Western blot was used to analyze the PEDF protein level 2 weeks after injection. Retinal flat mounts and immunohistochemistry were employed to analyze RGC survival and axon regeneration 2 weeks and 4 weeks after injection. The data were analyzed with one-way ANOVA in SPSS (version 19.0). A P
