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T.A. Walker, A.E. Faulkner, Y. Cheng, H. Yin, A. Fernandes, M.J. Phillips, S.L. Ball, A.Y. Chow, M.T. Pardue; Subretinal Implantation Induces Photoreceptor Preservation in RCS Rat Not Seen in Wild–Type Long Evans or S334ter Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5267.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Subretinal implantation of a microphotodiode array (MPA) induces neuroprotective effects on degenerating photoreceptors in an animal model of retinitis pigmentosa (RP) (Pardue et al., 2003; ARVO E–Abstract 5063). In order to understand the mechanisms underlying this effect, photoreceptor preservation was evaluated in rat models of RP resulting from two different mutations: 1) an RPE defect (RCS) and 2) a rhodopsin mutation with a moderate rate of degeneration similar to the RCS rat (S334ter, line 5), and a fast rate of degeneration (S334ter, line 3). Methods: Active or inactive MPAs were implanted subretinally near the beginning of photoreceptor degeneration in the RCS (P21) and the S334ter, lines 3 and 5 (P14) rats. Wild–type Long Evans (WT) rats were implanted as adults (P240) and followed for 8 weeks. Retinal function was monitored on a weekly or biweekly basis using electroretinography (ERG). RCS, S334ter line 3, and S334ter line 5 rats were euthanized at 8, 3, and 7 weeks post–implantation, respectively, and their eyes enucleated for histological processing and photoreceptor nuclei counts. Results: In each mutant rat, ERG b wave amplitude declined in both the active– and inactive–implanted eyes at the same rate as the unoperated eyes. In WT rats, there was a 20% decrease in b wave amplitude in implanted as compared to unoperated eyes. A significantly greater number of photoreceptors were counted over the active and inactive MPA in the RCS rats compared to the fellow unoperated RCS rat eyes. However, these differences were not seen in S334ter and WT rats in which the number of photoreceptors overlying the MPA was decreased. Conclusions: These results show that neuroprotection in RCS rats was associated with an active or inactive subretinal MPA. Conversely, in S334ter and WT rats the presence of a subretinal device was associated with photoreceptor cell loss directly overlying the implant. These differences suggest that neuroprotective mechanisms vary according to the specific type of retinal mutation.
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