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Abstract #8550 Published in IGR 5-1
Novel antisense oligonucleotides targeting TGF-β inhibit in vivo scarring and improve surgical outcome
Cordeiro MF; Mead AL; Ali RR; Alexander RA; Murray S; Chen C; York-Defalco C; Dean NM; Schultz GS; Khaw PTGene Therapy 2003; 10: 59-71
The scarring response is an important factor in many diseases throughout the body. In addition, it is a major problem in influencing the results of surgery. In the eye, for example, postoperative scarring can determine the outcome of surgery. This is particularly the case in the blinding disease glaucoma, where several anti-scarring regimens are currently being used to improve glaucoma surgery results, but are of limited use clinically because of severe complications. The authors have recently identified transforming growth factor-β (TGF-β) as a target for postoperative anti-scarring therapy in glaucoma, and now report the first study of novel second-generation antisense phosphorothioate oligonucleotides against TGF-β in vivo. Single applications of a TGF-β OGN at the time of surgery in two different animal models closely related to the surgical procedure performed in glaucoma patients, significantly reduced postoperative scarring (p < 0.05) and improved surgical outcome. These findings suggest that TGF-β antisense oligonucleotides have potential as a new therapy for reducing post-surgical scarring. Its long-lasting effects after only a single administration at the time of surgery make it particularly attractive clinically. Furthermore, although this agent has been shown to be useful in the eye, it could have widespread applications anywhere in the body where the wound-healing response requires modulation.
Dr. M.F. Cordeiro, Institute of Ophthalmology, Department of Pathology, Bath Street, London EC1V 9EL, UK
Classification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)
