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

Ideno,Junichi; Mizukami,Hiroaki; Kakehashi,Akihiro; Saito,Yuka; Okada,Takashi; Urabe,Masashi; Kume,Akihiro; Kuroki,Masatoshi; Kawakami,Masanobu; Ishibashi,Shun; Ozawa,Keiya

doi:10.3892/ijmm.19.1.75

January 2007 Volume 19 Issue 1

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January 2007 Volume 19 Issue 1

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Article

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

Authors:
- Junichi Ideno
- Hiroaki Mizukami
- Akihiro Kakehashi
- Yuka Saito
- Takashi Okada
- Masashi Urabe
- Akihiro Kume
- Masatoshi Kuroki
- Masanobu Kawakami
- Shun Ishibashi
- Keiya Ozawa
View Affiliations / Copyright

Affiliations: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi 329-0498, Japan
Pages: 75-79
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Published online on: January 1, 2007

https://doi.org/10.3892/ijmm.19.1.75
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Abstract

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 the 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.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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Abstract

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