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M. S. Klocek, J. W. Sassani, P. J. McLaughlin, I. S. Zagon; The Role of Opioid Growth Factor in Enhancing the Success of Trabeculectomy: In vitro Studies. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4147.
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Over 2.2 million people have glaucoma in the U.S. Trabeculectomy is commonly used to prevent complications of glaucoma, and the success of this procedure depends on the reaction of Tenon's capsule fibroblasts (TCFs) to the surgical trauma. A serious detriment of this filtration surgery is the hyperproliferation of TCFs. This study examined the presence and function of the inhibitory opioid growth factor (OGF) and its receptor (OGFr) in rabbit TCFs in vitro.
The presence and distribution of OGF in TCFs was determined by immunohistochemistry. OGFr was quantitated with radiolabeled OGF in receptor binding assays. The effects of OGF on growth were assessed in dose-response studies, and receptor mediation of OGF activity was ascertained by treatment with OGF and the short-acting opioid antagonist naloxone. The toxicity of OGF action was examined in reversibility experiments, as well as by evaluating apoptosis and necrosis. The specificity of OGF as an opioid involved with rabbit TCF growth was examined by neutralization with an antibody to OGF, whereas the tonic interaction of OGF with OGFr was explored using the potent and long-acting opioid antagonist naltrexone (NTX).
OGF and OGFr were detected in rabbit TCF cells in vitro. Receptor binding data revealed a one-site model of binding, with a binding capacity of 6.5 ± 0.8 fmol/mg protein and a binding affinity of 4.6 ± 1.4 nM. Rabbit TCFs treated with 10-7, 10-6, or 10-5 M OGF contained 28%, 33%, and 37%, respectively, fewer cells than controls at 72 hr (p<0.001). Rabbit TCFs treated for 72 hr with NTX or antibody to OGF had significant increases in cell number from control levels, demonstrating the tonic nature of OGF-OGFr interaction, and the specificity of OGF. Apoptosis or necrosis was not evident.
OGF and OGFr are present, and the OGF-OGFr axis functions to decrease rabbit TCF proliferation in a safe and non-toxic manner, suggesting a new non-toxic treatment to reduce fibrosis of filtration surgery for glaucoma and to eliminate the complications of other antifibrotic therapies.
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