Animal models of optic nerve diseases

Levkovitch-Verbin, Hani

doi:10.1038/sj.eye.6701576

Cited by 115 publications

(90 citation statements)

References 39 publications

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“…34 The injured axon of RGC triggers a degenerative response that spreads retrogradely to the soma. The death of RGCs is progressive because the primary damage is followed by a wave of secondary degeneration.…”

Section: Leukocytes Are Recruited To the Retina After Optic Nerve Injurymentioning

confidence: 99%

“…34 To determine whether retinal vascular inflammation occurs after optic nerve injury, we transplanted bone marrow (BM) cells from green fluorescence protein (GFP) transgenic mice (WT-GFP þ ) into irradiated WT mice to produce chimeric mice (WT-GFP þ /WT). These mice only expressed GFP in blood leukocytes, making it possible to specifically track leukocyte trafficking in retinal vessels in real time with an SLO.…”

Section: Role Of Cxcl10/cxcr3 Axis In Tonmentioning

confidence: 99%

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Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Liu

Zhu

et al. 2017

The American Journal of Pathology

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Traumatic optic neuropathy (TON) is an acute injury of the optic nerve secondary to trauma. Loss of retinal ganglion cells (RGCs) is a key pathological process in TON, yet mechanisms responsible for RGC death remain unclear. In a mouse model of TON, real-time noninvasive imaging revealed a dramatic increase in leukocyte rolling and adhesion in veins near the optic nerve (ON) head at 9 hours after ON injury. Although RGC dysfunction and loss were not detected at 24 hours after injury, massive leukocyte infiltration was observed in the superficial retina. These cells were identified as T cells, microglia/monocytes, and neutrophils but not B cells. CXCL10 is a chemokine that recruits leukocytes after binding to its receptor C-X-C chemokine receptor (CXCR) 3. The levels of CXCL10 and CXCR3 were markedly elevated in TON, and up-regulation of CXCL10 was mediated by STAT1/3. Deleting CXCR3 in leukocytes significantly reduced leukocyte recruitment, and prevented RGC death at 7 days after ON injury. Treatment with CXCR3 antagonist attenuated TON-induced RGC dysfunction and cell loss. In vitro co-culture of primary RGCs with leukocytes resulted in increased RGC apoptosis, which was exaggerated in the presence of CXCL10. These results indicate that leukocyte recruitment in retinal vessels near the ON head is an early event in TON and the CXCL10/CXCR3 axis has a critical role in recruiting leukocytes and inducing RGC death. (Am J Pathol 2017, 187: 352e365; http://dx

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Section: Leukocytes Are Recruited To the Retina After Optic Nerve Injurymentioning

confidence: 99%

Section: Role Of Cxcl10/cxcr3 Axis In Tonmentioning

confidence: 99%

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Liu

Zhu

et al. 2017

The American Journal of Pathology

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“…Studies conducted in rats and dogs for 1 month or 3 months showed that key target organs for adverse effects for both drugs were the gastrointestinal tract and the hematopoietic system (10,12,(43)(44)(45). However, tedizolid had plasma exposure multiples 4 to 8 times the human-equivalent plasma exposure without adverse effects, whereas linezolid toxicities were evident at drug plasma levels comparable with humanequivalent doses, with no adverse effect levels below the human therapeutic plasma exposure (Table 6) (10,12,43).…”

Section: Discussionmentioning

confidence: 99%

“…Doses were chosen with the intent to yield tedizolid plasma levels ranging from about one to eight times the systemic exposures achieved in patients at the therapeutic dose (200 mg once daily). The high doses of 30 mg/kg/ day (males) and 10 mg/kg/day (females) were the MTD levels previously determined in a 3-month rat toxicity study, in which higher doses were not tolerated and exceeded the MTD (12). In addition, because the main purpose of the study was to assess the potential of tedizolid to induce neuropathies using sensitive morphological techniques, it was not considered necessary to include linezolid as a comparator, for which peripheral and optic neuropathies already have been well documented in rats at human therapeutic plasma exposures (10).…”

Section: Methodsmentioning

confidence: 99%

“…Tedizolid was tested in a full battery of nonclinical safety studies to identify potential toxicities. No neuropathological effects were observed during routine animal toxicologic testing in studies up to 3 months in duration (12). To provide a more indepth assessment of the potential for tedizolid to cause neurotoxicity, a special neuropathology study that used sensitive morphological procedures was conducted with tedizolid in rats, a species used for general toxicologic testing and previously shown to be predictive of oxazolidinone-induced neuropathy (10).…”

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confidence: 99%

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Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months

Schlosser¹,

Hosako

Radovsky

et al. 2015

Antimicrob Agents Chemother

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Tedizolid, a novel oxazolidinone antibacterial, was administered to Long Evans rats by oral gavage once daily for up to 9 months at doses near the maximum tolerated dose (MTD) to evaluate for potential neurotoxicity. Mean plasma exposures of tedizolid at the low-, medium-, and high-dose levels (7.5, 15, and 30 mg/kg of body weight/day for males; 2.5, 5, and 10 mg/kg/day for females) were similar between males and females and were 1.8-, 3.9-, and 8.0-fold greater than exposures in patients at the therapeutic dose (200 mg once daily). Evaluated endpoints included survival, clinical observations, body weight, and food consumption. At 1, 3, 6, and 9 months, ophthalmic examinations, functional observational batteries, and locomotor activity measures were conducted, brain weights/sizes were recorded, and perfusion-fixed tissues were collected from 12 rats/sex/group/time point. A detailed morphological assessment was conducted on brain, eyes, optic nerve/tract, spinal cord, peripheral nerves (includes sciatic, sural, tibial, peroneal, trigeminal), and skeletal muscle. At the end of 9 months, less body weight gain was seen in high-dose males (؊6.7%) and females (؊5.8%) compared with that seen in controls. There were no tedizolid-related adverse neurobehavioral effects or tedizolid-related histopathologic changes in the central/peripheral nervous systems, including the optic nerve. Results of this study indicate that tedizolid was not neurotoxic when administered long term to pigmented rats at doses near the MTD, which were up to 8-fold higher than the human therapeutic exposure.

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Steroids for traumatic optic neuropathy

Yu‐Wai‐Man

Griffiths

2007

Cochrane Database of Systematic Reviews

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Animal models of optic nerve diseases

Cited by 115 publications

References 39 publications

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Critical Role of the CXCL10/C-X-C Chemokine Receptor 3 Axis in Promoting Leukocyte Recruitment and Neuronal Injury during Traumatic Optic Neuropathy Induced by Optic Nerve Crush

Lack of Neuropathological Changes in Rats Administered Tedizolid Phosphate for Nine Months

Steroids for traumatic optic neuropathy

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