**5. Conclusions**

From these observations, we conclude that targeted ablation of *Dhdds* selectively in RPE cells results in perturbation of DHDDS-dependent processes, resulting in structural and functional deficits in both the RPE and photoreceptors, in a manner resembling geographic atrophy. The degeneration progresses relatively slowly (compared to the rod-specific *Dhdds* ablation model) over the course of a few months, rather than weeks.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2073-4409/9/3/771/s1, Figure S1: Stitched images of *Dhddsflx*/*flx* and *Dhddsflx*/*flx* Cre RPE mouse retina, Figure S2: Fundus imaging and fluorescein angiography (FA), Figure S3: Contrast sensitivity and spatial frequency assessment in WT, *Dhddsflx*/*flx*, and *Dhddsflx*/*flx* Cre RPE mice, Video S1: Serial Block-Face Scanning Electron Microscopy of WT *Dhddsflx*/*flx*, Video S2: Serial Block-Face Scanning Electron Microscopy of region 1 of *Dhddsflx*/*flx* Cre RPE, Video S3: Serial Block-Face Scanning Electron Microscopy of region 2 of *Dhddsflx*/*flx* Cre RPE.

**Author Contributions:** Conceptualization, S.J.P., S.R.R., S.J.F. and M.L.D.; methodology, S.J.D., M.L.D., S.J.F., and S.J.P.; software, S.J.P., M.L.D., and T.W.K; validation, S.J.D., M.L.D., D.S., S.R.R., and S.J.P.; data curation, M.L.D., C.N., S.R.R., S.J.F. and S.J.P.; writing—original draft preparation, M.L.D., C.N., and S.J.P.; writing—review and editing, S.J.F., S.J.P., S.R.R., M.L.D., and D.S., visualization, S.J.P., S.R.R., and S.J.F.; supervision, T.W.K., S.J.F., and S.J.P.; project administration, S.J.F. and S.J.P.; funding acquisition, S.J.P. and S.J.F. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was supported by U.S.P.H.S. (National Institutes of Health/National Eye Institute) gran<sup>t</sup> R01 EY029341 to S.J.P. and S.J.F., support from the UAB Vision Science Research Center, and a core gran<sup>t</sup> P30 EY003039 to SJP, as well as facilities and resources provided by the VA Western NY Healthcare System (S.J.F., S.R.R.).

**Acknowledgments:** We thank Jeffrey Messinger for expert technical assistance with light level histology and TEM, Isaac Cobb for technical assistance with some of the experiments, Amy Stablewski (Roswell Park Cancer Institute (RPCI) Gene Targeting and Transgenic Facility) for the generation of *Dhddsflx*/*flx* mice, and Yun Le (University of Oklahoma Health Sciences Center) for generously providing the CreRPE mouse line. The opinions expressed herein do not reflect those of the Department of Veteran Affairs or the U.S. Government.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders of this study had no role in the design; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
