A laser-induced mouse model with long-term intraocular pressure elevation

Yun, H and Lathrop, KL and Yang, E and Sun, M and Kagemann, L and Fu, V and Stolz, DB and Schuman, JS and Du, Y (2014) A laser-induced mouse model with long-term intraocular pressure elevation. PLoS ONE, 9 (9).

Preview

PDF
Published Version
Available under License : See the attached license file.
Download (5MB)

Plain Text (licence)
Available under License : See the attached license file.
Download (1kB)

Abstract

Purpose: To develop and characterize a mouse model with intraocular pressure (IOP) elevation after laser photocoagulation on the trabecular meshwork (TM), which may serve as a model to investigate the potential of stem cell-based therapies for glaucoma. Methods: IOP was measured in 281 adult C57BL/6 mice to determine normal IOP range. IOP elevation was induced unilaterally in 50 adult mice, by targeting the TM through the limbus with a 532-nm diode laser. IOP was measured up to 24 weeks post-treatment. The optic nerve damage was detected by electroretinography and assessed by semiautomatic counting of optic nerve axons. Effects of laser treatment on the TM were evaluated by histology, immunofluorescence staining, optical coherence tomography (OCT) and transmission electron microscopy (TEM). Results: The average IOP of C57BL/6 mice was 14.5±2.6 mmHg (Mean ±SD). After laser treatment, IOP averaged above 20 mmHg throughout the follow-up period of 24 weeks. At 24 weeks, 57% of treated eyes had elevated IOP with the mean IOP of 22.5±2.5 mmHg (Mean ±SED). The difference of average axon count (59.0%) between laser treated and untreated eyes was statistically significant. Photopic negative response (PhNR) by electroretinography was significantly decreased. CD45+ inflammatory cells invaded the TM within 1 week. The expression of SPARC was increased in the TM from 1 to 12 weeks. Histology showed the anterior chamber angle open after laser treatment. OCT indicated that most of the eyes with laser treatment had no synechia in the anterior chamber angles. TEM demonstrated disorganized and compacted extracellular matrix in the TM. Conclusions: An experimental murine ocular hypertension model with an open angle and optic nerve axon loss was produced with laser photocoagulation, which could be used to investigate stem cell-based therapies for restoration of the outflow pathway integrity for ocular hypertension or glaucoma. Copyright:

Citation/Export:
Social Networking:	Share \|

Details

Item Type:

Article

Status:

Published

Creators/Authors:

Creators	Email	Pitt Username	ORCID
Yun, H
Lathrop, KL	Kira.Lathrop@pitt.edu	KLL21
Yang, E
Sun, M
Kagemann, L	lek19@pitt.edu	LEK19
Fu, V
Stolz, DB	donna.stolz@pitt.edu	DSTOLZ
Schuman, JS	jss28@pitt.edu	JSS28	0000-0002-8885-3766
Du, Y	yiqindu@pitt.edu	YIQINDU