title: A laser-induced mouse model with long-term intraocular pressure elevation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Yun
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kira L
authors.initials: KL
authors.lastname: Lathrop
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Enzhi
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Larry
authors.initials: L
authors.lastname: Kagemann
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Valeria
authors.initials: V
authors.lastname: Fu
authors.affiliation: Department of Cell Biology, Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
authors.affiliation: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Louis J. Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Du
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005901:Glaucoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000528:radiation effects*; D017075:Laser Coagulation; D008028:Light Coagulation; D051379:Mice; D009798:Ocular Hypertension / Q000503:physiopathology / Q000628:therapy; D009900:Optic Nerve / Q000473:pathology / Q000528:radiation effects; D033581:Stem Cell Transplantation; D014129:Trabecular Meshwork / Q000473:pathology / Q000528:radiation effects