Optic Neuropathy Due to Microbead-Induced Elevated Intraocular Pressure in the Mouse

Chen, Huihui; Wei, Xin; Cho, Kin‐Sang; Chen, Guochun; Sappington, Rebecca M.; Calkins, David J.; Chen, Dong F.

doi:10.1167/iovs.09-5115

Cited by 157 publications

(185 citation statements)

References 37 publications

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“…38 Briefly, mice were anesthetized by intraperitoneal injection of a ketamine (120 mg/kg) and xylazine (12 mg/kg) mixture (Phoenix Pharmaceutical, St. Joseph, MO) supplemented by topical proparacaine HCl (0.5%; Bausch & Lomb Pharmaceuticals, Tampa, FL). Elevation of IOP was induced unilaterally in adult wild-type C57BL/6J and Ngb-Tg mice by an anterior chamber injection of 10-m polystyrene microbeads (Molecular Probes; Invitrogen, Eugene, OR) that had been resuspended in PBS at a final concentration of 7.2 ϫ 10 6 beads/mL.…”

Section: Induction Of Chronic Iop Elevation In Micementioning

confidence: 99%

“…Elevation of IOP was induced unilaterally in adult wild-type C57BL/6J and Ngb-Tg mice by an anterior chamber injection of 10-m polystyrene microbeads (Molecular Probes; Invitrogen, Eugene, OR) that had been resuspended in PBS at a final concentration of 7.2 ϫ 10 6 beads/mL. 38 The right cornea was gently punctured with a 30-gauge needle without injuring the lens or iris. Through this entry wound, 2 L of microbeads were injected into the anterior chamber using a glass micropipette.…”

Section: Induction Of Chronic Iop Elevation In Micementioning

confidence: 99%

“…38 The measurement of IOP was conducted consistently at the same time in the morning. Mice were anesthetized by isoflurane inhalation (2% to 4%; Webster Veterinary, Devens, MA) that was delivered in 100% oxygen in a precision vaporizer.…”

Section: Iop Measurementmentioning

confidence: 99%

“…Tuj-1-positive cells were counted as described previously. 38,40 At least three nonoverlapping retinal sections of each eye were studied. Values are reported as means Ϯ SD.…”

Section: Detection Of Ngb Expression With Immunohistochemistrymentioning

confidence: 99%

“…Recently, we and others developed a convenient method of reproducibly inducing chronic IOP elevation in mice by anterior chamber injection of polystyrene microbeads. 37,38 With this mouse model, we investigated the functions of NGB in the retina and, using mouse genetic tools, demonstrated a role of NGB in promoting RGC survival by reducing oxidative stress and improving mitochondrial function in glaucoma. These findings offer a unique opportunity for neuroprotective interventions aimed at effective control of neuronal damage in glaucoma.…”

mentioning

confidence: 99%

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Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Wei

Cho

et al. 2011

The American Journal of Pathology

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Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Neuroglobin (NGB) is a novel member of the globin superfamily that is distantly related to hemoglobin and myoglobin. 1 A highly conserved protein in evolution, human and mouse Ngb, both comprised of 151 amino acids, are 94% identical. 2,3 In mammals, expression of NGB is found in the brain, retina, and other nerve tissues, predominantly in neurons but absent from glial cells. 4 -7 Distribution of NGB protein in the normal human retina is very similar to what has been described in mice: NGB is detected primarily in the plexiform layers and photoreceptor inner segments, which are rich in mitochondria and synapses and consume high amounts of oxygen. 8,9 NGB has been shown to act as an endogenous neuroprotective molecule that enhances neuronal survival under hypoxic-ischemic insults in the brain 10 -12 ; however, its physiological functions and molecular mode of actions are not fully understood. Of note, NGB is present at a 100-fold greater concentration in the retina than in the brain, 8,[13][14][15] suggesting that the retina may be its most important site of function; however, among the many unknown roles of NGB, functional significance of NGB expression in the retina has been largely unexplored.

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Section: Induction Of Chronic Iop Elevation In Micementioning

confidence: 99%

Section: Induction Of Chronic Iop Elevation In Micementioning

confidence: 99%

Section: Iop Measurementmentioning

confidence: 99%

“…Tuj-1-positive cells were counted as described previously. 38,40 At least three nonoverlapping retinal sections of each eye were studied. Values are reported as means Ϯ SD.…”

Section: Detection Of Ngb Expression With Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

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