cpfl1 mice undergo a progressive, selective degeneration of their dysfunctional cone photoreceptor cells over time. To analyze these morphologic changes in the retina, in vivo cSLO analyses were performed between postnatal weeks 4 and 8. Because only approximately 3% of the murine photoreceptors are cones and these are relatively widely spaced, it was unclear whether selective loss may lead to detectable changes in vivo. No differences between WT and
cpfl1 mice could be detected, either in native fundus imaging (green laser at 514 nm, infrared laser at 830 nm, and autofluorescence mode) or in indocyanine-green angiography (data not shown). In addition, no changes could be detected in
cpfl1 mice between 4 and 8 weeks of age (data not shown). In particular, no enhanced autofluorescence was observed that would have indicated a substantial accumulation of lipid-rich photoreceptor debris, presumably lipofuscin, remained after the degradation of photoreceptor cells.
10 To visualize cones specifically and to monitor the process of their degeneration in vivo, we cross-bred
cpfl1 mutants with RG-GFP transgenic mice. In this way, single cone cells were visible in the autofluorescence mode of the cSLO, and the changes in their number and distribution as part of the degenerative process in the
cpfl1 mutants were analyzed across ages in individual mice. The doubly mutant RG-GFP
cpfl1 mice initially displayed the same amount of GFP expression as their single RG-GFP counterparts at 3 weeks (
Fig. 4). However, there was a marked decrease in GFP expression over time, leading to an almost complete loss of GFP-expressing cells in the ventral region and a strong reduction in the dorsal region (
Fig. 4B) but no such change in RG-GFP animals (
Fig. 4A). Thus, RG-GFP expression in
cpfl1 mice allowed in vivo follow-up of the number and distribution of cone photoreceptors during the course of progressive, selective degeneration in the
cpfl1 mouse model.