Exogenous modulation of intrinsic optic nerve neuroprotective activity.
BACKGROUND
To characterize the molecular and functional status of the rat retina and optic nerve after acute elevation of intraocular pressure (IOP).


METHODS
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.


RESULTS
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.


CONCLUSIONS
Continuous release of neurotrophic growth factors (NGFs) significantly protects optic nerve function in the experimental model of retinal ischemia observed by PLR analysis.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. sgrozdan@iastate.edu
Sinisa D
SD
Grozdanic
Tatjana
T
Lazic
Markus H
MH
Kuehn
Matthew M
MM
Harper
Randy H
RH
Kardon
Young H
YH
Kwon
Erin B
EB
Lavik
Donald S
DS
Sakaguchi
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D020869:Gene Expression Profiling; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D007429:Intraocular Pressure; D019344:Lactic Acid; D008863:Microspheres; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009798:Ocular Hypertension / Q000150:complications / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D009900:Optic Nerve / Q000187:drug effects* / Q000378:metabolism; D009901:Optic Nerve Diseases / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D011914:Rats, Inbred BN; D020813:Receptor, trkB / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020813:Receptor, trkB