Abstract
Purpose :
Functional peroxisome proliferator activated receptor α (PPARα) activity contributes to the maintenance of emmetropization in chicks since a PPARα agonist, GW7647, suppressed experimental myopia development. We determined the role of PPARα function in maintaining normal ocular refractive power by evaluating the effects of loss of PPARα function on myopia development in two different transgenic PPARα knockout mice strains.
Methods :
Refractive development was measured with an eccentric infrared photorefractor in 4, 6 and 8 week old homozygous, heterozygous PPARα-knockout and wild-type (WT) littermate mice, respectively. Optical coherence tomography evaluated corneal thickness, anterior chamber depth, lens thickness, vitreous chamber depth and axial length (AL).
Results :
(1) PPARα-homozygous knockout mice developed relatively more myopia compared with their WT littermates and heterozygous counterparts. Furthermore, refractive error progression in heterozygous PPARα knockout mice was intermediate between that in knockout mice and WT counterparts at every age (4 weeks (W): PPARα-homozygous knockout mice -17.96±1.98D vs. heterozygous -10.35±1.10D vs. WT counterparts -6.68±1.37D; 6W: PPARα-homozygous knockout mice -13.01±2.10D vs. heterozygous -5.37±1.42D vs. WT counterpart -1.30±1.06D; 8W: PPARα-homozygous knockout mice -9.44±2.46D vs. heterozygous -3.28±1.56D vs. WT counterpart -1.95±0.87D). (2) AL of the homozygous knockouts was significantly shorter than that in WTs Furthermore, in the heterozygousmice, the AL change was intermediate between that in the homozygous knockouts and WT littermates (4W: PPARα-knockout mice 2.503±0.016mm vs. heterozygous 2.530±0.012mm vs. WT 2.579±0.012mm; 6W: PPARα-knockout mice 2.584±0.018mm vs. heterozygous 2.623±0.015mm vs. WT counterparts 2.656±0.012mm; 8W: PPARα-knockout mice 2.666±0.021mm vs. heterozygous counterparts 2.675±0.011mm vs. WT counterparts 2.708±0.013mm).
Conclusions :
PPARα activation in mice contributes to maintenance of emmetropization since the amount of myopia development in each age group was greater in PPARα transgenic KOs than that in WT mice. PPARα involvement in this process was substantiated by showing that in the homozygous knockouts myopia development was greater than that in the heterozygous knockouts.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.