Effect of Reduced Retinal VLC-PUFA on Rod and Cone Photoreceptors

Abstract

The VLC-PUFAs are important for rod, but not cone, function and for rod photoreceptor longevity.

Current Progress in Deciphering Importance of VLC-PUFA in the Retina

“…Despite the minimal decrease in VLC-PUFAs, Harkewicz et al (2012) found that Elovl4 C-cKO mice had decreased cone flicker responses at 7 months of age compared to WT mice. These results are contrary to Barabas et al (2013) and Bennett et al (2014b), who did not find cone dysfunction at 6 and 12 months, respectively.…”

“…This is obviated when the reduction of retinal VLC-PUFAs are considered (Table 20.1). These fatty acids were decreased by 36-97 % of WT values in the R-cKO and RC-cKO mice (Harkewicz et al 2012;Barabas et al 2013;Bennett et al 2014b;Marchette et al 2014). The VLC-PUFA levels in the cone-specific Elovl4 ablated mice (C-cKO) were unaffected (Table 20.1), but this could be due to the fact that mice are rod-dominant and that these fatty acids comprise only 12 % of the total fatty acids in the retina (Rotstein and Aveldano 1988).…”

“…Removal of Elovl4 expression in rods, cones, or both rods and cones has been achieved by breeding mice expressing Cre-recombinase driven by different photoreceptor specific promoters to Elovl4 flox/flox mice (Harkewicz et al 2012;Barabas et al 2013;Bennett et al 2014b;Marchette et al 2014). Cone-specific human redgreen pigment (HRGP)-Cre-and rod-specific Opsin-cre-or opsin-iCre75-expressing mice were used to delete Elovl4 from cones and rods, respectively, whereas Elovl4 was deleted from both photoreceptor types using Chx10-cre-expressing mice (Harkewicz et al 2012;Barabas et al 2013;Bennett et al 2014b).…”

“…Cone-specific human redgreen pigment (HRGP)-Cre-and rod-specific Opsin-cre-or opsin-iCre75-expressing mice were used to delete Elovl4 from cones and rods, respectively, whereas Elovl4 was deleted from both photoreceptor types using Chx10-cre-expressing mice (Harkewicz et al 2012;Barabas et al 2013;Bennett et al 2014b). A summary of the results from each study are provided in Table 20.1.…”

“…Harkewicz et al (2012) found R-cKO mice had decreased rod b-wave responses, but Barabas et al (2013) and Marchette et al (2014) did not find rod-mediated deficits in their 6-or 7-monthold R-cKO mice, respectively. When Elovl4 was deleted from both rods and cones (RC-cKO), retinal degeneration occurred and rod ERG responses were decreased in 12-month-old mice (Bennett et al 2014b). One possible explanation for the contradictory results could be the mosaic expression of Cre-recombinase, which resulted in varying degrees of Elovl4 ablation from rod cells.…”