April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
An AAV2 Vasoinhibin Vector Protects Against Increased Retinal Vasopermeability in Diabetic Rats
Author Affiliations & Notes
  • M. Ramirez
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Z. Wu
    Ocular Gene Therapy Laboratory, Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, Maryland
  • B. Moreno-Carranza
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • M. C. Jeziorski
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • G. Martinez de la Escalera
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • P. Colosi
    Ocular Gene Therapy Laboratory, Neurobiology Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, Maryland
  • C. Clapp
    Instituto de Neurobiologia, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Footnotes
    Commercial Relationships  M. Ramirez, None; Z. Wu, None; B. Moreno-Carranza, None; M.C. Jeziorski, None; G. Martinez de la Escalera, None; P. Colosi, None; C. Clapp, None.
  • Footnotes
    Support  SALUD-2008-C01-87015; National Eye Institute, NIH, USA. Z. Wu and P. Colosi.
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2526. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M. Ramirez, Z. Wu, B. Moreno-Carranza, M. C. Jeziorski, G. Martinez de la Escalera, P. Colosi, C. Clapp; An AAV2 Vasoinhibin Vector Protects Against Increased Retinal Vasopermeability in Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2526.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: : Proteolysis of the hormone prolactin generates vasoinhibins, a family of peptides that are able to inhibit the pathological increase in retinal vasopermeability (RVP) associated with diabetes (JCI 118:2291, 2008). Here, we tested the ability of an adeno-associated virus type-2 (AAV2) vasoinhibin vector to inhibit diabetes-induced RVP.

Methods: : AAV2 vectors expressing vasoinhibin, prolactin, or soluble VEGF receptor 1 (sFlt-1) (2.8 X 1010 vg/eye) were injected intravitreally into the eyes of rats. Four weeks later the animals were treated with streptozotocin to induce diabetes. After one month, RVP was evaluated using the Evans Blue dye method. RT-PCR of retinal extracts and Western blot analysis of the conditioned medium of vector-transduced HEK293 cells confirmed the expression and secretion of the various proteins encoded by the vectors.

Results: : In rats receiving intravitreal injection of vehicle, diabetes induced a significant increase in RVP compared to non-diabetic controls (49.0 ± 3.1 vs. 30.4 ± 2.9 µl plasma/g retina x h, p<0.001). This increase was prevented by intravitreal injection of the AAV2 vasoinhibin vector (29.1 ± 2.5 vs. 49.0 ± 3.1 µl plasma/g retina x h, p<0.001). In contrast, treatment with the AAV2 prolactin vector (44.3 ± 2.0 µl plasma/g retina x h, p<0.235) or the AAV2 sFlt-1 vector (37.5 ± 4.1 µl plasma/g retina x h, p<0.065) did not significantly block RVP in diabetic rats.

Conclusions: : These results suggest that AAV2 vasoinhibin vectors may have therapeutic value for controlling the pathological increase in RVP associated with diabetic retinopathy in the clinic.

Keywords: gene transfer/gene therapy • diabetic retinopathy • growth factors/growth factor receptors 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×