Abstract
Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of proliferative retinopathies and involves abnormal growth of blood vessels within and on the surface of the retina. In an effort to inhibit the formation of these aberrant blood vessels, we cloned an IGF-IR ribozyme into an expression vector that limits expression of the ribozyme to proliferating endothelial cells. An endothelin enhancer and Cdc6 promoter chimera drives expression of the IGF-IR ribozyme. This promoter limited retinal expression of the reporter gene to proliferating endothelial cells in two mouse models of proliferative retinopathy. In addition, expression of the IGF-IR ribozyme by this promoter inhibited aberrant retinal angiogenesis in both models while preserving normal vessels. These results demonstrate the feasibility of IGF-IR ribozyme expression in a selective manner for safer treatment of abnormal angiogenesis associated with retinopathy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 752-760 |
| Number of pages | 9 |
| Journal | Gene Therapy |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 2006 |
| Externally published | Yes |
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Keywords
- Endothelial
- IGF-I
- Proliferating
- Promoter
- Retinopathy
- Ribozyme
ASJC Scopus subject areas
- Genetics
Cite this
Proliferating endothelial cell-specific expression of IGF-I receptor ribozyme inhibits retinal neovascularization. / Shaw, L. C.; Pan, H.; Afzal, A.; Calzi, S. L.; Spoerri, P. E.; Sullivan, S. M.; Grant, M. B.
In: Gene Therapy, Vol. 13, No. 9, 05.2006, p. 752-760.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Proliferating endothelial cell-specific expression of IGF-I receptor ribozyme inhibits retinal neovascularization
AU - Shaw, L. C.
AU - Pan, H.
AU - Afzal, A.
AU - Calzi, S. L.
AU - Spoerri, P. E.
AU - Sullivan, S. M.
AU - Grant, M. B.
PY - 2006/5
Y1 - 2006/5
N2 - Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of proliferative retinopathies and involves abnormal growth of blood vessels within and on the surface of the retina. In an effort to inhibit the formation of these aberrant blood vessels, we cloned an IGF-IR ribozyme into an expression vector that limits expression of the ribozyme to proliferating endothelial cells. An endothelin enhancer and Cdc6 promoter chimera drives expression of the IGF-IR ribozyme. This promoter limited retinal expression of the reporter gene to proliferating endothelial cells in two mouse models of proliferative retinopathy. In addition, expression of the IGF-IR ribozyme by this promoter inhibited aberrant retinal angiogenesis in both models while preserving normal vessels. These results demonstrate the feasibility of IGF-IR ribozyme expression in a selective manner for safer treatment of abnormal angiogenesis associated with retinopathy.
AB - Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) are essential for normal ocular development and are expressed in numerous ocular cell types including lens epithelial cells, retinal pigment epithelial cells, Müller cells and endothelial cells. Endothelial cell proliferation is a common feature of proliferative retinopathies and involves abnormal growth of blood vessels within and on the surface of the retina. In an effort to inhibit the formation of these aberrant blood vessels, we cloned an IGF-IR ribozyme into an expression vector that limits expression of the ribozyme to proliferating endothelial cells. An endothelin enhancer and Cdc6 promoter chimera drives expression of the IGF-IR ribozyme. This promoter limited retinal expression of the reporter gene to proliferating endothelial cells in two mouse models of proliferative retinopathy. In addition, expression of the IGF-IR ribozyme by this promoter inhibited aberrant retinal angiogenesis in both models while preserving normal vessels. These results demonstrate the feasibility of IGF-IR ribozyme expression in a selective manner for safer treatment of abnormal angiogenesis associated with retinopathy.
KW - Endothelial
KW - IGF-I
KW - Proliferating
KW - Promoter
KW - Retinopathy
KW - Ribozyme
UR - http://www.scopus.com/inward/record.url?scp=33645999993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645999993&partnerID=8YFLogxK
U2 - 10.1038/sj.gt.3302718
DO - 10.1038/sj.gt.3302718
M3 - Article
C2 - 16437130
AN - SCOPUS:33645999993
VL - 13
SP - 752
EP - 760
JO - Gene Therapy
JF - Gene Therapy
SN - 0969-7128
IS - 9
ER -