Laser-induced ocular hypertension in albino CD-1 mice.
OBJECTIVE
To establish a laser-induced model of ocular hypertension (LIOH) in albino CD-1 mice and to characterize the sequence of pathologic events triggered by intraocular pressure (IOP) elevation.


METHODS
LIOH was induced unilaterally in CD-1 mice by laser photocoagulation of limbal and episcleral veins 270 degrees to 300 degrees circumferentially, sparing the nasal aspect and the long ciliary arteries. IOP was measured with a rebound tonometer. Hematoxylin and eosin-stained plastic sections were used for morphometric analysis of retinal layers, and retinal whole-mounts were immunostained with anti-Brn-3b to quantify retinal ganglion cell (RGC) gene expression ion and density. Axonal and myelin morphologies were characterized using appropriate antibodies, and axon counts were obtained from paraphenylenediamine-stained optic nerve sections.


RESULTS
LIOH resulted in IOP doubling within 4 hours after laser treatment, which returned to normal by 7 days. Axon degenerative changes, reactive plasticity, and aberrant regrowth were detected at the optic nerve head (ONH) as early as 4 days after treatment. By 7 days, axon number was significantly reduced in the myelinated optic nerve, with concurrent signs of myelin degradation. At 14 days, Brn-3b(+) RGC density was reduced, with neuronal loss confined to the RGC layer and no apparent effects on other retinal layers.


CONCLUSIONS
Laser photocoagulation of limbal and episcleral veins induces transient ocular hypertension in albino CD-1 mice. The ensuing retinal and optic nerve pathologic events recapitulated key features of glaucoma and placed ONH RGC axon responses as an early manifestation of damage. LIOH in albino mice may be useful as a mouse model to examine mechanisms of RGC and axon glaucomatous injury.
Fu
Christine T
CT
Neuroscience Graduate Program, Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143, USA. cfu@vision.ucsf.edu
Sretavan
David
D
D000818:Animals; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007429:Intraocular Pressure; D017075:Laser Coagulation / Q000009:adverse effects*; D016850:Limbus Corneae / Q000098:blood supply; D051379:Mice; D018613:Microscopy, Confocal; D009798:Ocular Hypertension / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009898:Optic Disk / Q000378:metabolism / Q000473:pathology; D009901:Optic Nerve Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012164:Retinal Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D012590:Sclera / Q000098:blood supply; D014065:Tonometry, Ocular; D014680:Veins / Q000601:surgery
D015415:Biomarkers