angiogenesis in viral immunoinflammatory lesions
DESCRIPTION
Angiogenesis in Viral Immunoinflammatory Lesions. Barry T. Rouse University of Tennessee Part 4. Does control of angiogenesis represent a smart approach to control stromal keratitis?. Problem: many factors to deal with. EMAP II Endothelial Monocyte Activating Polypeptide. - PowerPoint PPT PresentationTRANSCRIPT
Angiogenesis in Viral Immunoinflammatory
Lesions
Barry T. RouseUniversity of Tennessee
Part 4
Does control of angiogenesis represent a smart approach to
control stromal keratitis?
• Problem: many factors to deal with
EMAP IIEndothelial Monocyte Activating Polypeptide
• Cytokine with several effects on neovascularization – Apoptosis of vascular endothelial cells– Upregulates TNF receptors – so TNF
induces apoptosis– Activates tissue factors and blood clots
• Proinflammatory effects• Rationale - targets growing blood
vessels so should inhibit effects of several angiogenic factors
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EMAP II (ng/ml)
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EMAP II induces apoptosis in vascular endothelial cells in vitro and in vivo
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Control EMAP II
EMAP II suppresses neovascularization in murine HSK
D2 p.I.
D8 p.I.
D15 p.I.
HS
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EMAP II Suppresses HSK lesion score
Future approaches – possible siRNA targetingtargeting
multiple angiogenesis factors
Preliminary studyPreliminary study
• Plasmid encoding siRNA expressed following Plasmid encoding siRNA expressed following intra-stromal or sub-conjunctival injectionintra-stromal or sub-conjunctival injection
• Mixture of siRNA inhibiting VEGF and VEGF Mixture of siRNA inhibiting VEGF and VEGF receptors gave significant inhibition of receptors gave significant inhibition of
angiogenesis induced by CpGangiogenesis induced by CpG
Inhibition of CpG induced angiogenesis by siRNA delivery
CpG + siLacZ Day 4 CpG + siVEGF, R1, R2 Day 4
General Conclusions
• Herpes induced stromal keratitis an immunoinflammatory lesion
• Neovascularization a major step in pathogenesis
• HSV induces angiogenesis indirectly• Control of angiogenesis inhibits SK• Need multiple approaches for
satisfactory therapy
Colleagues Involved
• Dennis Klinman
• Margaret Schwartz
• Napoleone Ferrara
• Mei Zheng
• Bum-Seok Kim
• Kaustuv Banerjee
• Partha Biswas
• Sujin Lee