Adenovirus-mediated gene therapy for corneal clouding in mice with mucopolysaccharidosis type VII

Citation
Y. Kamata et al., Adenovirus-mediated gene therapy for corneal clouding in mice with mucopolysaccharidosis type VII, MOL THER, 4(4), 2001, pp. 307-312
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR THERAPY
ISSN journal
1525-0016 → ACNP
Volume
4
Issue
4
Year of publication
2001
Pages
307 - 312
Database
ISI
SICI code
1525-0016(200110)4:4<307:AGTFCC>2.0.ZU;2-6
Abstract
Recent advances in systemic treatments for mucopolysaccharidosis have led t o therapies that improve the multiple somatic features of this disease, but the therapeutic effect on ocular manifestations such as corneal clouding i s not satisfactory. Here, we administered an adenovirus expressing human be ta -glucuronidase (AxCAhGUS) into the anterior chamber or intrastromal regi on of the cornea in mice with mucopolysaccharidosis type VII (B6/MPSVII), a nd successfully treated corneal clouding of MPSVII. When we injected AxCAhG US into the anterior chamber of the eyes, cells expressing beta -glucuronid ase (GUSB) were located mainly in the trabecular meshwork as well as in all corneal regions, and subsequent pathological corrections in the cornea wer e achieved. Widespread transgene expression was also observed when we admin istered AxCAhGUS inside the cornea after lamellar keratotomy, and rapid eli mination of the lysosomal storage in the corneal keratocytes occurred. Furt hermore, intrastromal vector administration did not generate significant le vels of anti-adenovirus neutralizing antibodies, and secondary vector admin istration was effective. Based on these observations, we conclude that it i s worth developing a treatment strategy for corneal clouding in mucopolysac charidosis based on direct intraocular administration of adenoviral vectors .