Abstract
Purpose: :
Implantation of a subretinal microphotodiode array (MPA) preserves photoreceptors directly overlying the area of implantation in the RCS rat, but shows no effect in the S334ter rat model (Walker et al., 2005). Both rat strains are models of retinitis pigmentosa with distinct mutations: Mertk or rhodopsin, respectively. Due to the lack of RP rat models, the feasibility of implanting mouse models was tested to further examine the neuroprotective effects of MPA implantation on different forms of RP.
Methods: :
All mice were implanted randomly in one eye with a 0.5 mm diameter microphotodiode array (Optobionics Corp.) using the same surgical methods used for rat eyes. Wild–type C57BL/6J adult mice were implanted with an MPA device and retinal function measured with electroretinograms (ERG) biweekly until 8 weeks post–implantation. Mer mice, which share the same gene defect as the RCS rat, were implanted at 21 days of age and ERGs recorded each week until 4 weeks post–implantation. Eyes were enucleated for histological processing. Cell counts were calculated over the implant and across retinal locations.
Results: :
Implantation of C57BL/6J mice resulted in similar changes reported for other species with normal retinas: ERG responses were reduced immediately after surgery and then recovered while photoreceptors were lost immediately overlying the implant but were normal in all other retinal areas. In contrast, ERG responses from the mer mice increased from 2–3 weeks post–implantation and then decreased to match the contralateral control eye. While photoreceptors degenerated directly over the implant in the mer mice, photoreceptor nuclei were increased in all other retinal locations compared to controls.
Conclusions: :
Implantation of C57Bl/6J mice with the MPA device demonstrates the feasibility of subretinal implantation in the small mouse eye. Implantation of the MPA device in mer mice demonstrated a similar functional preservation pattern to RCS rats; however, the photoreceptor preservation motif seen in mer mice differed from RCS rats by promoting survival of photoreceptors not directly associated with the implantation site. To determine if the neuroprotective effects result from subretinal electrical stimulation versus mechanical injury in mer mice, future studies will compare results from mice implanted with active versus inactive devices.
Keywords: neuroprotection • retinal degenerations: hereditary • electroretinography: non-clinical