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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-4-27
pubmed:abstractText
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 (110?mmHg, 60?min) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1557-7422
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
559-65
pubmed:meshHeading
pubmed-meshheading:21175295-Animals, pubmed-meshheading:21175295-Electroretinography, pubmed-meshheading:21175295-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21175295-Eye Injuries, pubmed-meshheading:21175295-Eye Proteins, pubmed-meshheading:21175295-Gene Therapy, pubmed-meshheading:21175295-Gene Transfer Techniques, pubmed-meshheading:21175295-Genetic Vectors, pubmed-meshheading:21175295-Humans, pubmed-meshheading:21175295-In Situ Nick-End Labeling, pubmed-meshheading:21175295-Indoles, pubmed-meshheading:21175295-N-Methylaspartate, pubmed-meshheading:21175295-Nerve Growth Factors, pubmed-meshheading:21175295-Ocular Hypertension, pubmed-meshheading:21175295-Rats, pubmed-meshheading:21175295-Rats, Wistar, pubmed-meshheading:21175295-Retina, pubmed-meshheading:21175295-Retinal Ganglion Cells, pubmed-meshheading:21175295-Serpins, pubmed-meshheading:21175295-Simian immunodeficiency virus, pubmed-meshheading:21175295-Statistics, Nonparametric
pubmed:year
2011
pubmed:articleTitle
Pigment epithelium-derived factor gene therapy targeting retinal ganglion cell injuries: neuroprotection against loss of function in two animal models.
pubmed:affiliation
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't