Influence of rAAV-mediated antisense vascular endothelial growth factar165 RNA(rAAV-aVEGF 165) on diabetic retinopathy

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ZHOU Lian-hong(Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060,China)
CHEN jian()
ZHU Xiang-xiang(Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060,China)
Journal Title:
Volume 24, Issue 04, 2008
Key Word:
Diabetic retinopathy/therapy;Gene therapy;Vascular endothelial growth factors;Nucleotides;Diabetes mellitus, experimental

Abstract: Objective To observe the influence of rAAV-mediated antisense vascular endothelial growth factor (rAAV-aVEGF165) on the expression of retinal VEGF in diabetic rats. Methods 40 Sprague-Dawley rats induced diabetic rat model by intraperitoneal injection with streptozotocin (STZ). 32 rats were involved in study besides death and blood sugar recovery in experimental process, 16 spragud- Dawleg (SD) rats were received intravitreal injection with rAAV-aVEGF165 (1010 pfu) as experimental group, another group of Sprague-Dawleg (SD) rats were injected with phosphate buffered saline (PBS) as control group. One and five month after model establishment, the expression of retinal VEGF was evaluate by immunhistochemistry and Western blot; the retinal vasular was examined by transmission electron microscopy. Results On 1 month,the expression of retinal VEGF was lowest in each group. On 5 month, the expression of retinal VEGF was decreased in experimental group which compared to control, the difference are statistically significant (t=23.87, P < 0.01). The transmission electron microscopy results showed that retina has no obvious chages in experimental group, however,contral group showed fragmental thickening and splitting of basement membrane, swelling and deformation of endothelia cells, fingerlike prcess into the capillary cavity,and uneven distibution of heterochromatin in pericytes. Conclusion rAAV-aVEGF165 can reduce the expression of retinal VEGF thereby preventing occurrence and development of diabetic retinopathy, rAAV is an effective vectors of eye antisense gene.

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