April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
The Anti-Angiogenic Effect of Human Glial Derived Neurotrophic Factor: A Study Using a Novel Microsphere Delivery System
Author Affiliations & Notes
  • Matthew G. Trese
    Schepens Eye Research Institute, Boston, Massachusetts
    Department of Graduate Medical Sciences, Boston University, Boston, Massachusetts
  • Caio V. Regatieri
    Schepens Eye Research Institute, Boston, Massachusetts
    Dept. of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil
  • Budd A. Tucker
    Schepens Eye Research Institute, Boston, Massachusetts
  • Rocio Herrero-Vanrell
    Pharmaceutical Technology.School of Pharmacy,
    Complutense University, Madrid, Spain
  • Patricia Checa
    Pharm & Pharmaceutical Tech Sch,
    Complutense University, Madrid, Spain
  • Michael J. Young
    Schepens Eye Research Institute, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Matthew G. Trese, None; Caio V. Regatieri, None; Budd A. Tucker, None; Rocio Herrero-Vanrell, None; Patricia Checa, None; Michael J. Young, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4884. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: choroid: neovascularization • neuroprotection • drug toxicity/drug effects 

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