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E. B. Lavik, M. Voss Kyhn, K. Warfvinge, J. Folke Kiigaard, E. Scherfig, M. la Cour, H. Klassen, M. Young; Neuroprotection of Ischemic Injury in Pig Retina, Part III-- Functional Assessment. Invest. Ophthalmol. Vis. Sci. 2007;48(13):568.
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GDNF is neuroprotective for retinal ganglion cells. We sought to test whether sustained delivery of GDNF over 6 weeks could lead to improvements in function in a porcine model of acute retinal ischemia induced by transient low ocular perfusion pressure (OPP).Material and
A total of 9 animals were included in the study. A model of OPP was induced in pigs by monitoring and maintaining an IOP 5 mm Hg below the mean arterial pressure for 2 hours in the left eye. 3 days after OPP induction, a small vitrectomy was performed over the optic nerve head and 0.1 ml of either GDNF microspheres or blank microspheres in PBS at a concentration of 10 mg/ml were injected intravitreally in 7 pigs. Animals were evaluated with a slow-stimulation sequence mfERG-protocol at baseline before the low OPP procedure, at day 3 before injection of the microspheres and at days 14, 28 and 42 after injection of the microspheres. Another 2 animals received the injection without previous vitrectomy on the same day following the induction of the low OPP. mfERG was recorded at baseline before induction of low OPP and at day 21 after microsphere injection for these animals.
The induced components in the late mfERG responses were evaluated. A negative amplitude deflection (iN1) at approximately 50 ms was the most consistent finding. 3 days before the injection of microspheres, the iN1 amplitudes were reduced to 2 - 22% of the amplitude in the untreated eye. At the last day of examinations the iN1 amplitude were reduced to 16-47 % of the amplitude in the untreated eye in GDNF treatment compared to a reduction to 1-4% in blank controls (p=0.012).
The sustained delivery of GDNF in this model leads to improved function as compared to blank polymer controls. Taken with the results in parts I and II, we have developed a method which leads to degeneration of the RGCs. GDNF preserves the function of RGCs in this model suggesting a role for neuroprotection in the pig eye. This improved function correlates with the histology, and suggests that sustained delivery of GDNF may lead to functional neuroprotection in diseases affecting the optic nerve.
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