Abstract
Purpose:
Apolipoprotein A1 (ApoA1), the major component of high density lipoprotein, was suggested to be down-regulated in the retina of lens-induced myopia (LIM) animal model. The growth of axial length was reduced in LIM chicken possibly through an up-regulation of the ApoA1. Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is the first line therapy to regulate lipid metabolism by increasing the synthesis of ApoA1. The current study investigated the efficacy of fenofibrate on the growth of eye axial in lens-induced myopia chicken model.
Methods:
At 4-day old, male chicken was divided into different groups after gender determination by PCR method. In the LIM group, negative powered lenses (-10D) were worn on the right eyes and the left eyes were kept untreated as controls. In the treatment groups, 20uM, 100uM, 200uM fenofibrate delivered at an injection volume of 10ul, were injected into the bottom of the vitreous chamber of the right eye, and vehicle solutions were injected into the left eyes as control on day 5. Then, lenses (-10D) were worn on both eyes of treated chicken. An extra group of chicken without lens received 200uM fenofibrate intravitreal injection at the right eyes, and the left eyes were kept untreated as normal control. A high-frequency A-scan ultrasound system was used to measure the ocular parameters of all the chicken before the treatment and on day 8. Chicken with body weight growth abnormality or vitreous hemorrhage were ruled out. The changes of ocular parameters among different treated eyes were statistically analyzed by t-test.
Results:
Fenofibrate dose dependently suppressed the growth of ocular axial length, and statistical difference was recorded at the concentration of 200uM. On day 8, LIM chicken (n=15) treated by fenofibrate (200uM) had shorter axial length than LIM chicken (n=13) by 32.7% (P= 5.15078E-07). The fenofibrate showed no effect on the growth of ocular axial length of normal eyes. There was no different between fenofibrate treated eyes and LIM eyes at the choroid recovery changes after the negative lenses were taken off on day 8.
Conclusions:
200uM of Fenofibrate is protective against LIM development. The results not only demonstrate the therapeutic effects of fenofibrate on myopia, but they also support the possible role of PPARα-dependent mechanism in the development of myopia.