Exogenous modulation of intrinsic optic nerve neuroprotective activity

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Grozdanic, Sinisa
Lazic, Tatjana
Kuehn, Markus
Harper, Matthew
Kardon, Randy
Kwon, Young
Lavik, Erin
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Sakaguchi, Donald
Director of Biology and Genetics Undergraduate Program and Morrill Professor
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Veterinary Clinical Sciences
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The Graduate Program in Neuroscience is an interdepartmental and interdisciplinary training program at Iowa State University that offers the Master of Science and Doctor of Philosophy degrees. The Neuroscience training program offers a broad spectrum of Neuroscience research opportunities, ranging from the molecular to the cellular to the systems level of analysis. The program includes over 40 faculty from the departments of Biochemistry, Biophysics and Molecular Biology; Biomedical Sciences; Chemical and Biological Engineering; Ecology, Evolution, and Organismal Biology; Food Science and Human Nutrition; Genetics, Development and Cell Biology; Kinesiology; Mechanical Engineering; and Psychology.
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To characterize the molecular and functional status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP).


Retinal ischemia was induced in rats by increasing the IOP (110 mmHg/60 minutes). Microarray analysis, quantitative RT-PCR (qRT-PCR) and immunohistochemistry were used to characterize retinal tissue. PLGA microspheres containing neurotrophic factors (BDNF, GDNF, or CNTF) or empty microspheres were injected into the vitreous of operated animals 1 day after elevation of IOP. Pupil light reflex (PLR) parameters and electroretinograms (ERG) were monitored at multiple time points during the 60-day postoperative recovery period.


Molecular analysis showed a significant intrinsic up-regulation of CNTF at 10 and 25 days after induction of the acute ocular hypertension (p = 0.0067). Molecular tissue analysis of GDNF and its receptors (GDNFR1, GDNFR2), and BDNF and its receptor (trkB) showed no change in expression. Animals that received CNTF microspheres had no significant functional recovery compared to animals which received blank microspheres (p > 0.05). Animals that received GDNF or BDNF microspheres showed significant PLR recovery (p < 0.05 and p < 0.001 respectively) compared to non-treated animals.


Continuous release of neurotrophic growth factors (NGFs) significantly protects optic nerve function in the experimental model of retinal ischemia observed by PLR analysis.


This article is from Graefe's Archive for Clinical and Experimental Ophthalmology 248 (2010): 1105, doi: 10.1007/s00417-010-1336-7.