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Review
. 1999 Nov;83(11):1219-24.
doi: 10.1136/bjo.83.11.1219.

Molecular therapy in ocular wound healing

M F Cordeiro  1 , G S Schultz, R R Ali, S S Bhattacharya, P T Khaw
Affiliations
Review

Molecular therapy in ocular wound healing

M F Cordeiro et al. Br J Ophthalmol. 1999 Nov.
No abstract available

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Figures

Figure 1
Figure 1
Targets for molecular therapy. TGF-β activity can be inhibited in several ways using different molecular approaches. Therapy may be directed against TGF-β and receptor proteins using fully human neutralising monoclonal antibodies. Alternatively, inhibition of TGF-β and receptors at the level of gene expression is possible using antisense oligonucleotides or ribozymes, which act at the level of messenger RNA (mRNA) and prevent protein synthesis.
Figure 2
Figure 2
Phage antibodies. Fully human neutralising monoclonal antibodies can be made using the technique of phage display (Cambridge Antibody Technology, Melbourne UK). Human antibody light and heavy chains are identified from a large human antibody library. The human genes coding for these chains are then incorporated into a bacterial virus (phage) (A). When the phage infects a bacterium (usually, E coli), the bacterium makes the antibody protein which it displays on its surface (B). Specific clones binding to an antigen can then be amplified, and the whole antibody produced using recombinant methods (C).
Figure 3
Figure 3
Antisense oligonucleotides. Antisense molecules are synthetic oligonucleotides that have been designed to be complementary to mRNA strands that code for the production of specific proteins. The target mRNA is transcribed from DNA in the nucleus and, on entering the cytoplasm, is bound by the antisense molecule. The binding of the mRNA sense strand stops translation of the mRNA, and hence synthesis of the protein.
Figure 4
Figure 4
Gene transfer. Gene therapy depends on the successful transfer and delivery of the agents to specific tissues. A DNA vector—for example, a plasmid vector, which includes gene sequences for the target, a viral derived promoter, and a reporter can transfect cells in the target tissue.
Figure 5
Figure 5
Gene transfer in cornea. Using our rabbit model,34 we show transduction of the corneal epithelium with a DNA plasmid expressing a CAT reporter gene has occurred, as detected with Texas red immunostaining (5 µm section, ×20 magnification)
Figure 6
Figure 6
Gene transfer in conjunctiva. Using our mouse model of conjunctival scarring,33 we have shown that there is transduction of fibroblasts and mononuclear cells in the subconjunctival space with an AV vector expressing a lacZ reporter gene (AV.CMV.LacZnuc). Positive expression is indicated by galactosidase activity seen as blue (nuclear fast red counterstain, 5 µm section, ×80 magnification).
Figure 7
Figure 7
Ribozymes. Ribozymes are RNA molecules that are able enzymatically to cleave specific RNA bonds. Like antisense oligonucleotides, they can be designed to target any mRNA of specific proteins. The cleavage of mRNA by the ribozyme leads to inhibition of translation and protein production.
See this image and copyright information in PMC

References

    1. Nat Med. 1998 Aug;4(8):967-71 - PubMed
    1. Invest Ophthalmol Vis Sci. 1999 Aug;40(9):1975-82 - PubMed
    1. J Neurooncol. 1998 Sep;39(3):237-44 - PubMed
    1. Exp Eye Res. 1998 Oct;67(4):395-401 - PubMed
    1. Int J Mol Med. 1998 Apr;1(4):657-63 - PubMed

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