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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).

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Abstract

© 2014 Yun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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:


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yun, H
Lathrop, KLkll21@pitt.eduKLL21
Yang, E
Sun, M
Kagemann, Llek19@pitt.eduLEK19
Fu, V
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Schuman, JSjss28@pitt.eduJSS280000-0002-8885-3766
Du, Yyiqindu@pitt.eduYIQINDU
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBui, Bang VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Center for Biologic Imaging
Other Centers, Institutes, or Units > Louis J. Fox Center for Vision Restoration
Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 1 September 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0107446
Schools and Programs: School of Medicine > Cell Biology
School of Medicine > Developmental Biology
School of Medicine > Ophthalmology
Swanson School of Engineering > Bioengineering
Refereed: Yes
Other ID: NLM PMC4162591
PubMed Central ID: PMC4162591
PubMed ID: 25216052
Date Deposited: 08 May 2015 15:39
Last Modified: 04 Feb 2019 15:58
URI: http://d-scholarship.pitt.edu/id/eprint/24018

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