Opposing Effects of PPARα Agonism and Antagonism on Refractive Development and Form Deprivation Myopia in Guinea Pigs.
Invest Ophthalmol Vis Sci
; 59(15): 5803-5815, 2018 12 03.
Article
em En
| MEDLINE
| ID: mdl-30521668
ABSTRACT
Purpose:
To determine if drug-induced peroxisome proliferator-activated receptor α (PPARα) signal pathway modulation affects refractive development and myopia in guinea pigs.Methods:
Pigmented guinea pigs were randomly divided into normal vision (unoccluded) and form deprivation myopia (FDM) groups. Each group received daily peribulbar injections of either a vehicle or (1) PPARα agonist, GW7647, clofibrate, or bezafibrate or (2) PPARα antagonist, GW6471, for 4 weeks. Baseline and posttreatment refraction and ocular biometric parameters were measured. Immunofluorescent staining of PPARα and two of its downstream readouts, cytosolic malic enzyme 1 (ME1) and apolipoproteinA II (apoA-II), was undertaken in selected scleral sections. Western blot analysis determined collagen type I expression levels.Results:
GW6471 induced a myopic shift in unoccluded eyes, but had no effect on form-deprived eyes. Conversely, GW7647 inhibited FDM progression without altering unoccluded eyes. Bezafibrate and clofibrate had effects on refraction similar to those of GW7647 in unoccluded and form-deprived eyes. GW6471 downregulated collagen type I expression in unoccluded eyes whereas bezafibrate inhibited collagen type I decreases in form-deprived eyes. GW6471 also reduced the density of ME1- and apoA-II-stained cells in unoccluded eyes whereas bezafibrate increased apoA-II-positive cell numbers in form-deprived eyes.Conclusions:
As GW7647 and GW6471 had opposing effects on myopia development, PPARα signaling modulation may be involved in this condition in guinea pigs. Fibrates are potential candidates for treating myopia since they reduced both FDM and the associated axial elongation. Bezafibrate also inhibited form deprivation-induced decreases in scleral collagen type I expression and the density of apoA-II expressing cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Refração Ocular
/
Privação Sensorial
/
PPAR alfa
/
Modelos Animais de Doenças
/
Miopia
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China