Effects of adenoviral-mediated gene transfer of interleukin-10, interleukin-4, and transforming growth factor-β on the survival of axotomized retinal ganglion cells
Section snippets
Optic nerve transection and retrograde labeling
Adult, female Sprague–Dawley rats (225–250 g; Charles River), that were free of common pathogens and housed in a Level B pathogen free environment, were used in all experiments. Animals were cared for according to the guidelines of the Canadian Council on Animal Care. All efforts were made to minimize animal suffering and to use only the number of animals necessary to produce reliable scientific data. Rats were anesthetized with i.p. injections of 7% chloral hydrate (420 mg/kg of body weight)
Transfection of retinal cells following intraocular or superior collicular injection of Ad.lacZ
The majority of transfected cells, after intraocular injection of Ad.lacZ, were Müller glial cells (Fig. 1a). Müller cell somata in the inner nuclear layer (INL) their radial processes that terminated in the inner limiting membrane and outer limiting membrane were β-gal positive. The transfection rate of retinal Müller cells after intraocular Ad.lacZ injection averaged to approximately 0.6%. Retinal NFL astrocytes were also transfected by intraocular Ad.lacZ injection (Fig. 1b); however, only
Discussion
In the present study we compared the effects of three anti-inflammatory cytokines, IL-10, IL-4, and TGF-β on the survival of axotomized RGCs. Our results demonstrate that prolonged delivery of IL-10 or IL-4 by gene transfer to the retina or retrograde transport from the s.c. enhances the survival of axotomized RGCs. We also showed that IL-10 or IL-4 gene transfer decreases the density of ED1 positive monocytes/macrophages in the NFL after optic nerve transection. Prolonged administration of
Acknowledgements
This work was supported by a Natural Sciences and Engineering Research Council of Canada operating grant OGP0171190 to A.K.B. P.D.K. is supported by a studentship from the Ontario Neurotrauma Foundation.
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