Schuettauf Frank, Vorwerk Christian, Naskar Rita, Orlin Anton, Quinto Kristine, Zurakowski David, Dejneka Nadine S, Klein Ronald L, Meyer Edward M, Bennett Jean
Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
Curr Eye Res. 2004 Dec;29(6):379-86. doi: 10.1080/02713680490517872.
Brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) hold much promise for the protection of retinal ganglion cells against excitotoxic cell death. We tested the possibility of delivering these growth factors to retinal ganglion cells via an adeno-associated viral (AAV) vector and tested their efficacy in two models of excitotoxicity.
Rat retinas were infected with AAV vectors encoding bFGF or BDNF. A control vector containing green fluorescent protein (GFP) was injected in the contralateral eye. Eyes were subjected to either an intravitreal injection of N-methyl-D-aspartate (NMDA) or optic nerve crush, and ganglion cell survival was evaluated.
AAV.CMV.bFGF and AAV.CBA.BDNF were neuroprotective against NMDA injection 1 month post-treatment. Additionally, AAV.CMV.bFGF was protective against optic nerve crush.
AAV-mediated delivery of bFGF and BDNF can promote retinal cell survival following excitotoxic insult.
脑源性神经营养因子(BDNF)和碱性成纤维细胞生长因子(bFGF)在保护视网膜神经节细胞免受兴奋性毒性细胞死亡方面具有很大潜力。我们测试了通过腺相关病毒(AAV)载体将这些生长因子递送至视网膜神经节细胞的可能性,并在两种兴奋性毒性模型中测试了它们的功效。
用编码bFGF或BDNF的AAV载体感染大鼠视网膜。将含有绿色荧光蛋白(GFP)的对照载体注射到对侧眼。对眼睛进行玻璃体内注射N-甲基-D-天冬氨酸(NMDA)或视神经挤压,并评估神经节细胞的存活率。
治疗1个月后,AAV.CMV.bFGF和AAV.CBA.BDNF对NMDA注射具有神经保护作用。此外,AAV.CMV.bFGF对视神经挤压具有保护作用。
AAV介导的bFGF和BDNF递送可促进兴奋性毒性损伤后视网膜细胞的存活。