Gene transfer of soluble TGF-beta type II receptor inhibits experimental proliferative vitreoretinopathy.
This study was conducted to investigate a method of gene therapy for proliferative vitreoretinopathy (PVR) by inhibiting type beta transforming growth factor (TGF-beta). PVR was induced in pigmented rabbits by intravitreal injection of 50 000 rabbit conjunctival fibroblasts after vitrectomy. Subsequently, the eyes received an intravitreal application of adenovirus vector encoding a soluble type II TGF-beta receptor (AdTbeta-ExR, n = 10) or adenoviral vector expressing beta-galactosidase (AdLacZ) (n = 10) or balanced salt solution (BSS) (n = 6). The eyes were examined ophthalmoscopically for 28 days after surgery, and the clinical stage of PVR was evaluated on a scale of zero to five. Histological examinations were performed on the treated eyes on day 28. All control eyes injected with AdLacZ or BSS developed PVR, characterized by retinal detachment and the formation of intravitreal membranes within 7 days. The eyes injected with AdTbeta-ExR also developed features of PVR, but the average severity from day 5 to day 28 was significant lower than in the control eyes (P < 0.05). TGF-beta plays an important role in PVR progression in a PVR model, and prevention of TGF-beta signaling could be therapeutically useful.
Oshima
Y
Y
Department of Ophthalmology, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Sakamoto
T
T
Hisatomi
T
T
Tsutsumi
C
C
Ueno
H
H
Ishibashi
T
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005654:Fundus Oculi; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D017346:Protein Serine-Threonine Kinases; D011817:Rabbits; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014822:Vitreous Body / Q000737:chemistry / Q000473:pathology
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II