Gene Therapy for Ocular Neovascularization

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in pre-clinical studies. Most of the studies has conducted with different adeno-associate serotype vectors. In addition, Adeno and lentivirus vectors have been used. Therapy has targeted to block vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded phase 2 trials further.

Download Full-text

Potential long-term inhibition of ocular neovascularization by recombinant adeno-associated virus-mediated secretion gene therapy. Lai YKY, Shen WY, Brankov M, Lain CM, Constable IJ, Rakoczy PE. Gene Therapy 2002;9:804–813.Dr. Y.K.Y. Lai, Department of Molecular Ophthalmology/Lions Eye Institute, 2 Verdun Street, Nedlands 6009, Western Australia, Australia.

American Journal of Ophthalmology ◽

10.1016/s0002-9394(02)02041-x ◽

2003 ◽

Vol 135 (1) ◽

pp. 127

Keyword(s):

Gene Therapy ◽

Western Australia ◽

Adeno Associated Virus ◽

Ocular Neovascularization

Download Full-text

Gene therapy for ocular neovascularization: a cure in sight

Current Opinion in Genetics & Development ◽

10.1016/s0959-437x(03)00043-1 ◽

2003 ◽

Vol 13 (3) ◽

pp. 317-322 ◽

Cited By ~ 12

Author(s):

Samuel J Reich ◽

Jean Bennett

Keyword(s):

Gene Therapy ◽

Ocular Neovascularization

Download Full-text

Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye

Pharmaceutics ◽

10.3390/pharmaceutics13020219 ◽

2021 ◽

Vol 13 (2) ◽

pp. 219

Author(s):

Sanna Koponen ◽

Emmi Kokki ◽

Kati Kinnunen ◽

Seppo Ylä-Herttuala

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

Vision Loss ◽

Viral Vector ◽

Great Promise ◽

Vascular Endothelial ◽

Ocular Neovascularization ◽

Vessel Growth ◽

Lentivirus Vectors ◽

Endothelial Growth Factors

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in preclinical studies. Most of the studies have been conducted with different adeno-associated serotype vectors. In addition, adeno- and lentivirus vectors have been used. Therapy has been targeted towards blocking vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded further than Phase 2 trials.

Download Full-text

Long-term Evaluation of AAV-Mediated sFlt-1 Gene Therapy for Ocular Neovascularization in Mice and Monkeys

Molecular Therapy ◽

10.1016/j.ymthe.2005.04.022 ◽

2005 ◽

Vol 12 (4) ◽

pp. 659-668 ◽

Cited By ~ 81

Author(s):

Chooi-May Lai ◽

Wei-Yong Shen ◽

Meliha Brankov ◽

Yvonne K.Y. Lai ◽

Nigel L. Barnett ◽

...

Keyword(s):

Gene Therapy ◽

Ocular Neovascularization ◽

Term Evaluation

Download Full-text

Gene therapy for ocular angiogenesis

Clinical Science ◽

10.1042/cs20020314 ◽

2003 ◽

Vol 104 (6) ◽

pp. 561-575 ◽

Cited By ~ 30

Author(s):

James W. B. BAINBRIDGE ◽

Ajay R. MISTRY ◽

Adrian J. THRASHER ◽

Robin R. ALI

Keyword(s):

Gene Expression ◽

Gene Therapy ◽

Gene Transfer ◽

Adverse Effects ◽

Age Related Macular Degeneration ◽

Large Animal ◽

Central Feature ◽

Adeno Associated Virus ◽

Ocular Neovascularization ◽

Age Related

Ocular neovascularization is a central feature of diabetic retinopathy and age-related macular degeneration. These conditions are the major causes of blindness in the developed world. Current treatments are of limited efficacy and associated with significant adverse effects. Characterization of the molecular and cellular events involved in angiogenesis has led to the identification of a number of angiostatic molecules with potential therapeutic value. The systemic administration of small molecule angiostatic proteins risks significant systemic adverse effects and the effect of their intraocular injection is short-lived. Local gene transfer, however, offers the possibility of targeted, sustained and regulatable delivery of angiostatic proteins to the retina after a single procedure to introduce a vector to an intraocular site. The effect of intra-ocular delivery of recombinant viruses carrying genes encoding angiostatic proteins has been demonstrated in rodent models of ocular neovascularization. Recombinant adeno-associated virus-mediated local gene transfer of a vascular endothelial growth factor inhibitor controls both retinal and choroidal neovascularization. The clinical application of this approach may require the means to regulate gene expression in order to minimize the potential for adverse effects. Regulation of transgene expression by means of a hypoxia-responsive promoter offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the management of ischaemia-induced ocular neovascularization. Preclinical studies of gene transfer in a large animal model following subretinal delivery of a recombinant adeno-associated virus vector have demonstrated efficient sustained reporter gene expression in cells of the outer retina. Recent progress has enabled the planning of clinical trials of gene therapy for ocular neovascular disorders.

Download Full-text