EIAV vector-mediated delivery of endostatin or angiostatin inhibits angiogenesis and vascular hyperpermeability in experimental CNV.

This research article investigates the use of equine infectious anaemia virus (EIAV) vectors encoding endostatin and angiostatin to inhibit the growth of blood vessels and control leakage from vessels in a mouse model of choroidal neovascularisation, a key feature of age-related macular degeneration. The results show significant reductions in both factors, suggesting potential for this approach in treating human patients with the condition.

Objective of the study

• The objective of the study was to evaluate the effectiveness of gene therapy using vectors based on the equine infectious anaemia virus (EIAV). These vectors were engineered to express endostatin or angiostatin, proteins known to prevent the formation of new blood vessels (a process known as angiogenesis) and the increased permeability of these vessels.

Experimental design

• The vectors were injected into the subretinal space in a strain of mice called C57Bl/6J.
• The effectiveness of this therapy was assessed in a laser-induced model of choroidal neovascularisation (CNV), which involves the abnormal growth of blood vessels in the part of the eye responsible for sharp vision.
• The spread of CNV and vascular permeability were measured with fluorescein angiograms, which uses a fluorescent dye and a specialized camera to visualize the blood flow in the retina.

Results of the study

• The use of EIAV.endostatin resulted in a 59.5% reduction in CNV area and a reduction in hyperpermeability of 25.6%.
• EIAV.angiostatin led to a 50.0% reduction in CNV area and a 23.9% reduction in hyperpermeability.
• Compared to controls, EIAV.endostatin increased the frequency of cell death within the CNV area.
• No negative effects were observed in the retina or retinal vasculature due to the injection of EIAV vector or the expression of endostatin or angiostatin.

Conclusion

• This study suggests that EIAV-based vectors encoding endostatin or angiostatin effectively control abnormal blood vessel growth and leakage in experimental CNV, and carry no long-term harmful effects. This supports their potential use in managing patients with exudative age-related macular degeneration, a major cause of blindness in older adults.