Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa.
Cell Rep
; 15(2): 372-85, 2016 Apr 12.
Article
en En
| MEDLINE
| ID: mdl-27050517
ABSTRACT
Most retinitis pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nighttime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE) and, thus, is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment-rich outer segments (OSs), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Retinitis Pigmentosa
/
Células Fotorreceptoras Retinianas Conos
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos