advertisement
Abstract #45967 Published in IGR 13-2
Pigment epithelium-derived factor gene therapy targeting retinal ganglion cell injuries: Neuroprotection against loss of function in two animal models
Miyazaki M; Ikeda Y; Yonemitsu Y; Goto Y; Murakami Y; Yoshida N; Tabata T; Hasegawa M; Tobimatsu S; Sueishi KHuman Genetics and Therapeutics 2011; 22: 559-565
Lentiviral vectors are promising tools for the treatment of chronic retinal diseases including glaucoma, as they enable stable transgene expression. We examined whether simian immunodeficiency virus (SIV)-based lentiviral vector-mediated retinal gene transfer of human pigment epithelium-derived factor (hPEDF) can rescue rat retinal ganglion cell injury. Gene transfer was achieved through subretinal injection of an SIV vector expressing human PEDF (SIV-hPEDF) into the eyes of 4-week-old Wistar rats. Two weeks after gene transfer, retinal ganglion cells were damaged by transient ocular hypertension stress (110mmHg, 60min) and N-methyl-d-aspartic acid (NMDA) intravitreal injection. One week after damage, retrograde labeling with 4',6-diamidino-2-phenylindole (DAPI) was done to count the retinal ganglion cells that survived, and eyes were enucleated and processed for morphometric analysis. Electroretinographic (ERG) assessment was also done. The density of DAPI-positive retinal ganglion cells in retinal flat-mounts was significantly higher in SIV-hPEDF-treated rats compared with control groups, in both transient ocular hypertension and NMDA-induced models. Pattern ERG examination demonstrated higher amplitude in SIV-hPEDF-treated rats, indicating the functional rescue of retinal ganglion cells. These findings show that neuroprotective gene therapy using hPEDF can protect against retinal ganglion cell death, and support the potential feasibility of neuroprotective therapy for intractable glaucoma.
Y. Ikeda. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku Fukuoka 812-8582, Japan. Email: ymocl@pathol1.med.kyushu-u.ac.jp
Classification:
11.9 Gene therapy (Part of: 11 Medical treatment)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
