Treatment of adult neural progenitor cells prior to transplantation affects graft survival and integration in a neonatal and adult rat model of selective retinal ganglion cell depletion

Article type: Research Article

Authors: Mellough, Carla B. | Cui, Qi | Harvey, Alan R.

Affiliations: School of Anatomy & Human Biology, The University of Western Australia, 35 Stirling Hwy, Crawley, Perth 6009, WA, Australia

Note: [] Corresponding author: Professor Alan Harvey, Chair, UWA Neuroscience Discipline Group, School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Tel.: +61 8 6488 3294; Fax: +61 8 6488 1051; E-mail: [email protected]

Abstract: Purpose: We tested whether microenvironmental changes surrounding apoptotic neural degeneration, cellular pre-treatment and timing of transplant can influence the survival and differentiation of transplanted cells. This was done by transplanting adult hippocampal precursor cells (AHPCs) into normal and retinal ganglion cell (RGC) depleted rat retinae. Methods: Apoptotic RGC death was induced in neonates by removal of the contralateral superior colliculus (SC) and in adults by unilateral optic nerve transection, with or without a peripheral nerve (PN) graft. AHPCs were transplanted 24 h after SC ablation, or 5, 7 or 14 days following optic nerve (ON) transection. Hosts received untreated grafts, or grafts treated by co-culture with embryonic retinal explants or the neuropeptide somatostatin. Results: AHPCs integrated within all neonatal and 65% of adult retinae. Greater numbers of AHPCs were observed within the ganglion cell layer (GCL) in SC lesioned hosts. Explant co-culture induced proliferation of grafted AHPCs within host retinae. Somatostatin-treatment resulted in reduced overall engraftment but increased integration within the GCL. In lesioned adults, greatest GCL engraftment was observed following 7 or 14 day grafts. Some AHPCs in the inner retina expressed neuronal antigens and extended processes into the ON. Conclusions: These data indicate that various factors can influence the behaviour of grafted cells and work towards encouraging the functional restoration of retinal circuitry.

Keywords: Adult hippocampal progenitors, ganglion cell depletion, optic nerve transection, retinal transplantation

Journal: Restorative Neurology and Neuroscience, vol. 25, no. 2, pp. 177-190, 2007