Histological and morphometric evaluation of transient retinal and optic nerve ischemia in rat.
Non-arteritic anterior ischemic optic neuropathy is caused by a transient optic nerve ischemia and results in permanent vision loss. Currently, there is no effective treatment for this ischemic optic nerve injury. This study characterized the duration and extent of ischemia induced after a coagulopathy injury to the optic nerve of adult rats. Acute ischemia was induced in adult rats by intravenous injection of Rose Bengal dye, followed by argon green laser treatment of the vessels at the optic disc. Rats were assessed in the short-term for hypoxyprobe-1 binding and expression of hypoxia inducible factor-1alpha (HIF-1 alpha) and fractin, markers of neuronal injury. Five months after injury, optic axon number was quantified. The coagulopathy injury resulted in short-term hypoxia in the optic nerve and retina. Tissues were hypoxic within 15 min of the coagulopathy injury, but normoxic by 24 h as measured by hypoxyprobe-1 staining. Both HIF-1alpha and fractin were upregulated in ganglion cells variably across the retina. Five months after the ischemic injury, there was a 71% reduction in optic axon number compared to controls. It is critical to have a reproducible and relevant method for producing transient hypoxia in order to test therapeutic strategies for rescuing injured neurons. The coagulopathy induced in this study resulted in a reproducible and transient ischemic optic nerve injury and long-term axonal loss. This ischemia shows similar, although not identical, morphological and physiological changes to those seen in the human eye after optic nerve ischemia. We are currently testing therapeutic strategies to protect ganglion cells from degeneration after this ischemic injury.
Danylkova
Nataliya O
NO
Department of Ophthalmology, University of Minnesota, Minneapolis, 55455, USA.
Pomeranz
Howard D
HD
Alcala
Sandra R
SR
McLoon
Linda K
LK
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D015415:Biomarkers; D001778:Blood Coagulation Disorders / Q000503:physiopathology; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D005456:Fluorescent Dyes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007511:Ischemia / Q000139:chemically induced / Q000503:physiopathology*; D007834:Lasers; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D012171:Retinal Vessels / Q000503:physiopathology*; D012395:Rose Bengal; D016019:Survival Analysis; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D005456:Fluorescent Dyes; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012395:Rose Bengal