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R. Ejstrup, J. Kiilgaard, B. Tucker, H. Klassen, M. J. Young, M. la Cour; Pharmacokinetics of Intravitreal Glial Cell Line-Derived Neurotrophic Factor: Experimental Studies in Pigs. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6234.
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To establish the intravitreal pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) in porcine eyes under near physiological conditions (general anesthesia.)
In 12 pigs 24 eyes were injected intravitreally with 100 ng of GDNF. An injection solution of 500 µg/ml in pbs was prepared. After paracenthesis of 0.2 ml of aqueous humor from the anterior chamber 0.2 ml of injection solution was administered intravitreally with a 30G needle. Postoperative complications and intraocular pressure were assessed by indirect ophthalmoscopy and bimanual palpation after the procedure. Enucleation of eyes was performed at either 1h, 2h, 3h, 6h, 1day or 2 days postoperatively. Eyes were immediately dissected and all vitreous was collected and frozen. The vitreous samples were prepared by sonification and spinning before the GDNF content was determined by enzyme-linked immunosorbent assay (ELISA.)
At the early time points (1, 2 and 3h) limited distribution of GDNF was noted and great variability of the GDNF concentrations between samples existed. The lowest values were obtained from the 1h samples. At later time points GDNF was cleared from the vitreous with an estimated half life of 1.5 day. Assuming first-order decay a mathematical extrapolation was done that predicted levels of GDNF to be greater than the minimal detectable concentration of the ELISA for 9 days. None of the 12 eyes showed any complications.
In the pig intravitreal injection of pure GDNF appears to be safe and intravitreally administered GDNF is equally distributed in the vitreous six hours post injection. GDNF has a half life of 1.5 day in the porcine vitreous which is about half that of ranibizumab even though it is less than one third of its molar mass. Comparisons with vitrectomized porcine eyes should be undertaken to help determine the role of the vitreous body in clearance of GDNF.
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