Daniels Dru M, Shen Wei-Yong, Constable Ian J, Rakoczy P Elizabeth
Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia.
Clin Exp Ophthalmol. 2003 Oct;31(5):439-44. doi: 10.1046/j.1442-9071.2003.00693.x.
Recombinant adeno-associated virus (rAAV) is one of the most promising recombinant viral vectors for delivering therapeutic agents to the retina. The present study aims to quantify any effect that an rAAV construct may have on the retina. To be able to use rAAV for therapeutic purposes, the potentially toxic effect of the vector and an associated green fluorescent protein (gfp) marker has to be investigated.
By combining histological analysis with computer scanning techniques, the local toxicity of rAAV and gfp can be measured. This will have obvious implications for its role as a carrier in the rapidly developing world of gene therapy.
It is shown that a construct consisting of rAAV and gfp, delivered subretinally to rat eyes, causes no more histological damage than injection with saline alone. Furthermore, via fluorescent fundus photography and computer scanning techniques it is seen that the area exposed to the rAAV-gfp construct is significantly greater than the area of histological change.
It is thus concluded that the rAAV-gfp construct has no significant toxic effect, at an anatomical level, on the retina 12 months after injection.
重组腺相关病毒（rAAV）是将治疗剂递送至视网膜最有前景的重组病毒载体之一。本研究旨在量化rAAV构建体可能对视网膜产生的任何影响。为了能够将rAAV用于治疗目的，必须研究载体及相关绿色荧光蛋白（gfp）标记物的潜在毒性作用。
通过将组织学分析与计算机扫描技术相结合，可以测量rAAV和gfp的局部毒性。这对于其在迅速发展的基因治疗领域作为载体的作用具有明显意义。
结果表明，视网膜下注射到大鼠眼中的由rAAV和gfp组成的构建体，所造成的组织学损伤并不比单独注射生理盐水更多。此外，通过荧光眼底摄影和计算机扫描技术可以看出，暴露于rAAV-gfp构建体的区域明显大于组织学变化的区域。
因此得出结论，注射12个月后，rAAV-gfp构建体在解剖学水平上对视网膜没有明显的毒性作用。
