Müller glia-derived PRSS56 is required to sustain ocular axial growth and prevent refractive error.
PLoS Genet
; 14(3): e1007244, 2018 03.
Article
de En
| MEDLINE
| ID: mdl-29529029
ABSTRACT
A mismatch between optical power and ocular axial length results in refractive errors. Uncorrected refractive errors constitute the most common cause of vision loss and second leading cause of blindness worldwide. Although the retina is known to play a critical role in regulating ocular growth and refractive development, the precise factors and mechanisms involved are poorly defined. We have previously identified a role for the secreted serine protease PRSS56 in ocular size determination and PRSS56 variants have been implicated in the etiology of both hyperopia and myopia, highlighting its importance in refractive development. Here, we use a combination of genetic mouse models to demonstrate that Prss56 mutations leading to reduced ocular size and hyperopia act via a loss of function mechanism. Using a conditional gene targeting strategy, we show that PRSS56 derived from Müller glia contributes to ocular growth, implicating a new retinal cell type in ocular size determination. Importantly, we demonstrate that persistent activity of PRSS56 is required during distinct developmental stages spanning the pre- and post-eye opening periods to ensure optimal ocular growth. Thus, our mouse data provide evidence for the existence of a molecule contributing to both the prenatal and postnatal stages of human ocular growth. Finally, we demonstrate that genetic inactivation of Prss56 rescues axial elongation in a mouse model of myopia caused by a null mutation in Egr1. Overall, our findings identify PRSS56 as a potential therapeutic target for modulating ocular growth aimed at preventing or slowing down myopia, which is reaching epidemic proportions.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Troubles de la réfraction oculaire
/
Régulation de l'expression des gènes au cours du développement
/
Oeil
/
Protéases à sérine
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Female
/
Humans
/
Male
Langue:
En
Journal:
PLoS Genet
Sujet du journal:
GENETICA
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique