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Abstract #15583 Published in IGR 1-3
Molecular therapy in ocular wound healing.
Cordeiro MF; Schultz GS; Ali RR; Bhattacharya SS; Khaw PTBritish Journal of Ophthalmology 1999; 83 :1219-24
An important overview on molecular therapy and ocular wound healing was written by Francesca Cordeiro and colleagues from the group around Peng Khaw. The review discusses ocular woundhealing in general and particular molecular and cellular events in wound healing. The role of transforming growth factor beta is considered but also that of antisense oligonucleotides and ribozymes. To day it seems possible to create fully human neutralizing monoclonal antibodies. The outcome of clinical trials in animals is very positive and results in humans will soon be known. The authors discuss the modifications of gene expression and the use of antisense oligonucleotides to counteract the role of intra-cellular messenger RNA. Three modes of molecular treatment are also discussed: gene replacement, gene control, and gene addition. A major drawback in the development of effective clinical protocols involving gene therapy has been the disappointing efficiency of gene transfer and expression in patients. Compared with other tissues the eye is an easily accessible target for gene therapy. Different gene delivery systems are discussed, both viral and non-viral. The main disadvantage of the current generation of non-viral factors that they only allow short-term gene expression and generally limited to 3 days. It is hoped that adeno associated virus vectors may provide gene expression for several months. Ribozymes enzymatically cleave specific bonds in RNA molecules. The advantage of ribozymes is that they are not as concentration and time dependent. This group is studying the effect of ribozymes to the TGF-beta-2 receptor. The authors conclude that molecular biology offers exciting prospects for the modulation of wound healing in the eye. Advances in gene delivery and designs of antisense molecules and ribozymes offer the potential of more specific, safer, focal, and titratable treatment, with far reaching clinical applications. The reader is advised to read this article in full.
Dr.MF Cordeiro, Wound Healing Research and Glaucoma Units, Dep. of Pathology, Dep. of Molecular Genetics, Moorfields Eye Hospital and Institute of Ophthalmology, Bath Street, London EC1V 9EL
Classification:
12.8.10 Woundhealing antifibrosis (Part of: 12 Surgical treatment > 12.8 Filtering surgery)