Successful Photoreceptor Transplantation Into the Aged Ccl2/Mcp-1 Mouse Model of Age-Related Macular Degeneration

Abstract

Purpose: : Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and leads in both the wet and the dry form to loss of macular photoreceptors. Photoreceptor replacement by transplantation is therefore a potential future therapeutic strategy. It is not yet known whether transplanted photoreceptors can integrate into the aged retina.Therefore, we analysed the efficiency of photoreceptor transplantation in aged compared with young adult recipient mice. The Ccl2/MCP-1 knockout mouse has been described as a model for age related retinal disorders. With age, these mice develop phenotypic features similar to those seen in human AMD, including Drusen and atrophy of photoreceptors. In addition they show impaired macrophage recruitment to sites of injury and as macrophages have also been suggested to play a role in AMD pathogenesis we were interested to see if photoreceptors could be transplanted into the aged retina of Ccl-2/MCP-1 knockout mice.

Methods: : Rod precursors were isolated from Nrl.GFP mice at postnatal day 4. After dissociation, 200 000 cells were transplanted into the subretinal space in animals from four different groups (wt, 2 month (n=6); Ccl-2 ko, 2 month (n=6); wt 20 month (n=5); ccl2 ko, 20 month (n=6)). After three weeks the eyes were enucleated and processed for sectioning. The number of GFP positive, integrated cells per retina was determined.

Results: : Between 100 and 4000 integrated rod photoreceptor cells were found in young and aged wildtype retinas showing no significant difference between these two groups. In young and aged Ccl2/MCP-1 knockout mice a similar range of integrated cell numbers were seen and no significant change was observed between age-matched controls and Ccl2/MCP-1 knockout mice.

Conclusions: : These results show that the absence of the Ccl2/ MCP-1 cytokine in recipient retinas does not prevent rod photoreceptor integration and that the age of the recipient retina does not have a detrimental effect on rod photoreceptor transplantation. This observation is promising when considering photoreceptor transplantation as a future potential treatment for AMD.

Keywords: transplantation • age-related macular degeneration • aging