Prevention of diabetic retinopathy by intraocular soluble flt-1 gene transfer in a spontaneously diabetic rat model

Junichi Ideno, Hiroaki Mizukami, Akihiro Kakehashi, Yuka Saito, Takashi Okada, Masashi Urabe, Akihiro Kume, Masatoshi Kuroki, Masanobu Kawakami, Shun Ishibashi, Keiya Ozawa
2007 International Journal of Molecular Medicine  
The number of patients suffering from diabetes mellitus is constantly rising worldwide, and diabetic retinopathy (DR) has become the most frequent cause of postnatal blindness. Vascular endothelial growth factor (VEGF) is known to play a central role during DR development. Thus, inhibiting the effects of VEGF may hamper the disease progression, and gene transfer of the soluble VEGF receptor sflt-1 is an attractive approach for this purpose. However, the lack of suitable animal models hindered
more » ... e evaluation of this strategy. Recently, the spontaneously diabetic non-obese Torii (SDT) rat was established and is considered as one of the ideal models for human DR. In this study, we evaluated the efficacy of gene therapy in SDT rats by using adeno-associated viral vectors (AAV-sflt-1) injected into the subretinal space. Thirty weeks later, the progression of DR was assessed by fluorescein angiography using three parameters; the presence of an avascular area, extensive hyperfluorescein and arterial narrowing. These changes were significantly less evident in the 'treated' eyes than in the control. No adverse effects were observed throughout the study. These results indicate that local sflt-1 gene transfer inhibits DR progression in SDT rats and offers powerful therapeutic potential for the management of human DR.
doi:10.3892/ijmm.19.1.75 fatcat:jvj5l45sbbdpvc64xo4bp5tp3a