Avtor/Urednik | Cahoon, Judd M.; Rai, Ruju R.; Carroll, Lara S.; Uehara, Hironori; Zhang, Xiaohui; O'Neil, Christina L.; Medina, Reinhold J.; Das, Subrata Kumar; Muddana, Santhos K.; Križaj, David | |
Naslov | Intravitreal AAV2.COMP-Ang1 prevents neurovascular degeneration in a murine model of diabetic retinopathy | |
Tip | članek | |
Vol. in št. | Letnik 64, št. 2 | |
Leto izdaje | 2015 | |
Obseg | str. 4247-4259 | |
ISSN | 0012-1797 - Diabetes | |
Jezik | eng | |
Abstrakt | Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here, we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable with nondiabetic controls. In late DR, AAV2.COMP-Ang1 enhanced the therapeutic benefit of intravitreally delivered endothelial colony-forming cells by promoting their integration into the vasculature and thereby stemming further visual decline. AAV2.COMP-Ang1 single-dose gene therapy can prevent neurovascular pathology, support vascular regeneration, and stabilize vision in DR. | |
Proste vsebinske oznake | neurovascular degeneration diabetic retinopathy murine model žovčno-mišična degeneracija diabetična retinopatija model na glodalcih |