Recombinant angiostatin prevents retinal neovascularization in a murine proliferative retinopathy model

Gene Therapy
P I MenesesR M Duvoisin

Abstract

Retinal neovascularization is central to the pathogenesis of proliferative diabetic retinopathy, the leading cause of blindness among the middle-aged population. Angiostatin, a proteolytic fragment of plasminogen is one of the most promising inhibitors of angiogenesis currently in clinical trials. Here we show that recombinant angiostatin can inhibit retinal neovascularization in a mouse model of proliferative retinopathy. Because proliferative diabetic retinopathy is a recurrent disease, effective therapy will need to be sustained. Recombinant adeno-associated viruses permit long-term expression of transfected genes; however, they can only accommodate a small insert sequence. Thus, we engineered and tested a shortened recombinant angiostatin derivative containing a signal sequence to permit secretion. Recombinant protein was purified from the medium of transfected HEK293 cells and injected subcutaneously into treated animals. The retinal vasculature was analyzed in retinal flat mounts and using immunohistochemically stained sections. Both methods demonstrate that this short, secreted form of angiostatin is effective in reducing the development of blood vessels in a nontumor environment and has therapeutic potential for neovasc...Continue Reading

References

Apr 16, 1998·Diabetes Care·L P AielloR Klein
Aug 26, 1999·The New England Journal of Medicine·F L FerrisL M Aiello

❮ Previous
Next ❯

Citations

Oct 25, 2003·Progress in Retinal and Eye Research·Arup Das, Paul G McGuire
Jul 11, 2003·Progress in Retinal and Eye Research·Ray F Gariano
Nov 9, 2001·Drug Discovery Today·Henrik S. RasmussenLisa Wei
Sep 16, 2003·Retina·John R HeckenlivelyBo Chang
Jun 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Brian J RaislerWilliam W Hauswirth
Jan 17, 2007·Expert Opinion on Biological Therapy·Mariacarmela AlloccaAlberto Auricchio
Nov 1, 2006·Progress in Retinal and Eye Research·Sarah X Zhang, Jian-xing Ma
Jan 6, 2006·Journal of the American Society of Nephrology : JASN·Sarah X ZhangJian-Xing Ma
Aug 29, 2006·Oncogene·H HelmboldW Bohn
Apr 20, 2005·Oncogene·Maria A Ciemerych, Peter Sicinski
Feb 3, 2005·Oncogene·Maya Ameyar-ZazouaJonathan B Weitzman
Sep 6, 2019·International Journal of Molecular Sciences·Jessica K W TsangAmy C Y Lo
Nov 7, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tetyana LevchenkoLars Holmgren
Feb 27, 2016·Current Opinion in Ophthalmology·Robert B Garoon, J Timothy Stout

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Brian J RaislerWilliam W Hauswirth
Seminars in Ophthalmology
J C Lamkin, L J Singerman
Canadian Medical Association Journal
R L Holliday
Seminars in Ophthalmology
D Le, R P Murphy
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift für Augenheilkunde
Liu JianXu Wen
© 2021 Meta ULC. All rights reserved