Exogenous modulation of intrinsic optic nerve neuroprotective activity

Sinisa D Grozdanic; Tatjana Lazic; Markus H Kuehn; Matthew M Harper; Randy H Kardon; Young H Kwon; Erin B Lavik; Donald S Sakaguchi

doi:10.1007/s00417-010-1336-7

Back

Exogenous modulation of intrinsic optic nerve neuroprotective activity

Journal article

Open access

Peer reviewed

Exogenous modulation of intrinsic optic nerve neuroprotective activity

Sinisa D Grozdanic, Tatjana Lazic, Markus H Kuehn, Matthew M Harper, Randy H Kardon, Young H Kwon, Erin B Lavik and Donald S Sakaguchi

Graefe's archive for clinical and experimental ophthalmology, Vol.248(8), pp.1105-1116

08/2010

DOI: 10.1007/s00417-010-1336-7

PMCID: PMC3678383

PMID: 20229104

View Online

Abstract

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.

Brain-Derived Neurotrophic Factor - genetics

Reperfusion Injury - etiology

Oligonucleotide Array Sequence Analysis

Ocular Hypertension - physiopathology

Glial Cell Line-Derived Neurotrophic Factor Receptors - metabolism

Ocular Hypertension - complications

Gene Expression Profiling

Retinal Ganglion Cells - metabolism

Ciliary Neurotrophic Factor - administration & dosage

Microspheres

Rats, Inbred BN

Glial Cell Line-Derived Neurotrophic Factor - metabolism

Ciliary Neurotrophic Factor - genetics

Optic Nerve Diseases - metabolism

Brain-Derived Neurotrophic Factor - metabolism

Neuroprotective Agents - administration & dosage

Fluorescent Antibody Technique, Indirect

Disease Models, Animal

Electroretinography

Cell Survival

Intraocular Pressure

Lactic Acid

Polyglycolic Acid

Glial Cell Line-Derived Neurotrophic Factor - genetics

Rats

Nerve Growth Factors - administration & dosage

Reverse Transcriptase Polymerase Chain Reaction

Glial Cell Line-Derived Neurotrophic Factor - administration & dosage

Optic Nerve Diseases - genetics

Brain-Derived Neurotrophic Factor - administration & dosage

Ciliary Neurotrophic Factor - metabolism

Animals

Optic Nerve Diseases - prevention & control

Reperfusion Injury - physiopathology

Optic Nerve - drug effects

Receptor, trkB - metabolism

Retinal Ganglion Cells - drug effects

Optic Nerve - metabolism

Details

Title: Subtitle: Exogenous modulation of intrinsic optic nerve neuroprotective activity
Creators: Sinisa D Grozdanic - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. sgrozdan@iastate.edu
Tatjana Lazic
Markus H Kuehn
Matthew M Harper
Randy H Kardon
Young H Kwon
Erin B Lavik
Donald S Sakaguchi
Resource Type: Journal article
Publication Details: Graefe's archive for clinical and experimental ophthalmology, Vol.248(8), pp.1105-1116
DOI: 10.1007/s00417-010-1336-7
PMID: 20229104
PMCID: PMC3678383
NLM abbreviation: Graefes Arch Clin Exp Ophthalmol
ISSN: 0721-832X
eISSN: 1435-702X
Publisher: Germany
Grant note: R01 EY019485 / NEI NIH HHS EY019485 / NEI NIH HHS EY019294 / NEI NIH HHS R01 NS044007 / NINDS NIH HHS NS044007 / NINDS NIH HHS R01 EY019294 / NEI NIH HHS
Language: English
Date published: 08/2010
Academic Unit: Iowa Neuroscience Institute; Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983979990502771

Metrics

22 Record Views

12 Times Cited - Web of Science