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Matthew G. Trese, Caio V. Regatieri, Budd A. Tucker, Rocio Herrero-Vanrell, Patricia Checa, Michael J. Young; The Anti-Angiogenic Effect of Human Glial Derived Neurotrophic Factor: A Study Using a Novel Microsphere Delivery System. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4884.
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Recent research suggests that routine intraocular injections of anti-angiogenic drugs may damage retinal neurons. It is, therefore imperative to investigate new drugs and drug delivery systems which mitigate choroidal angiogenesis, protect retinal neurons and reduce the frequency of intraocular injections. Infusible bioinert microspheres slowly release their contents and have the potential to reduce the number of intraocular injections a patient must endure. Glial derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) are neuroprotectants that are thought to possess anti-angiogenic properties. This study aims to evaluate both a novel drug delivery system and the anti-angiogenic effect of GDNF and BDNF.
The ability of endothelial cells to form capillary-like structures in vitro when plated on top of a reconstituted basement membrane extracellular matrix (Matrigel) was investigated in cells treated with GDNF infused microspheres (40 and 80 µg/mL) or GDNF+BDNF infused microspheres (40 µg/mL respectively). MTT assays were performed to evaluate the cytotoxicity of these compounds in both retinal pigment epithelial cells (ARPE19) and endothelial cell (EC) cultures.
Both 40 and 80 µg/mL doses of GDNF infused microspheres caused a significant decrease (P< 0.05) in total length of tubes formed by endothelial cells in Matrigel. Additionally a significant decrease in capillary-like tube formation was observed in cell cultures exposed to GDNF+BDNF infused microspheres. MTT analysis showed no detectable cytotoxic effect in either ARPE19 or EC cultures. This study also demonstrates the viability of a bioinert microsphere drug delivery system.
This study shows that GDNF, either alone or in combination with BDNF, does indeed possess an anti-angiogenic effect. There was no discernible difference between GDNF infused microspheres at 40 or 80 µg/mL, therefore it seems the lower dosage could potentially suppress angiogenesis. This study also showed that bioinert microspheres are an effective vehicle for the delivery of a single or a combination of compounds. Finally, these results imply that the dual function of GDNF and BDNF may be important in the management of neovascular retinal disease.
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