A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Weina; Watson, Brant D.; Goldberg, Jeffrey L.

doi:10.1001/2013.jamaophthalmol.271

Cited by 25 publications

(18 citation statements)

References 50 publications

(57 reference statements)

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“…While there are a number of models of optic nerve damage (optic nerve crush 12 , optic nerve transection 13 , and PION 14 ), the rNAION model is humane, adaptable to both rats and mice. It more closely resembles the human clinical condition of NAION.…”

Section: Discussionmentioning

confidence: 99%

The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rNAION)

Guo

Mehrabian

Bernstein

2016

JoVE

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Nonarteritic anterior ischemic optic neuropathy (NAION) is a focal ischemic lesion of the optic nerve that affects 1/700 individuals throughout their lifetime. NAION results in optic nerve edema, selective loss of the retinal ganglion cell neurons (RGCs) and atrophy of the optic nerve. A rodent model of NAION that expresses most NAION features and sequelae has been developed, which is applicable to both rats and mice. This model utilizes a focal laser application of 532 nm wavelength to illuminate a photoactive dye, Rose Bengal (RB), to cause capillary damage and leakage at the targeted anterior optic nerve (the laminar region). After rNAION induction, there is an early optic nerve ischemia, optic nerve edema, and intraneural inflammation, followed by selective RGC and axonal loss. Since the optic nerve is a CNS white matter tract, the rNAION model is applicable to mechanistic studies of selective white matter ischemia, as well as neuroprotective analyses and short and long-term mechanisms of glial and neuronal response to ischemia.

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Section: Discussionmentioning

confidence: 99%

The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rNAION)

Guo

Mehrabian

Bernstein

2016

JoVE

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“…Three days after the NMDA injections, retrograde labeling of RGCs with FluoroGold (FG), in a manner similar to that described previously, 37,38 was performed to assess whether tranylcypromine influenced the survival of RGCs. Briefly, after each animal was deeply anesthetized with an intraperitoneal injection of a 1:1 mixture of xylazine hydrochloride (4 mg/kg; Bayer HealthCare) and ketamine hydrochloride (10 mg/kg; Daiichi Sankyo Propharma Co., Ltd.), its head fur was shaved and the skin was incised along the midline to expose the skull and sagittal, coronal, and transverse sutures.…”

Section: Retrograde Labeling To Detect the Survival Of Rgcsmentioning

confidence: 99%

Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells via p38 MAPK Activity

Tsutsumi

Iwao

Hayashi

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Tsutsumi T, Iwao K, Hayashi H, et al. Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38 MAPK activity. Invest Ophthalmol Vis Sci. 2016;57:6461-6473. DOI:10.1167/ iovs.16-19494 PURPOSE. The epigenetic mechanisms associated with ocular neurodegenerative diseases remain unclear. The present study aimed to determine the role of lysine-specific demethylase 1 (LSD1), which represses transcription by removing the methyl group from methylated lysine 4 of histone H3, in retinal ganglion cell (RGC) survival, and to investigate the details of the neuroprotective mechanism of tranylcypromine, a major LSD1 inhibitor. METHODS.The authors evaluated whether tranylcypromine contributes to neuronal survival following stress-induced damage using primary cultured rat RGCs and in vivo N-methyl-Daspartate (NMDA)-induced excitotoxicity. Additionally, the molecules associated with tranylcypromine treatment were assessed by microarray and immunoblot analysis. RESULTS.Tranylcypromine significantly suppressed neuronal cell death following glutamate neurotoxicity and oxidative stress. Microarray and immunoblot analyses revealed that p38 mitogen-activated protein kinase (MAPK)c was a key molecule involved in the neuroprotective mechanisms induced by tranylcypromine because the significant suppression of p38 MAPKc by glutamate was reversed by tranylcypromine. Moreover, although pharmacologic inhibition of the phosphorylation of the total p38 MAPKs interfered with neuroprotective effects of tranylcypromine, the specific inhibition of p38 MAPKa and p38 MAPKb did not influence RGC survival. This suggests that the non-p38 MAPKa/b isoforms have important roles in neuronal survival by tranylcypromine. Additionally, the intravitreal administration of tranylcypromine significantly saved RGC numbers in an in vivo glaucoma model employing NMDA-induced excitotoxicity.CONCLUSIONS. These findings indicate that tranylcypromine-induced transcriptional and epigenetic regulation modulated RGC survival via the promotion of p38 MAPKc activity. Therefore, pharmacologic treatments that suppress LSD1 activity may be a novel therapeutic strategy that can be used to treat neurodegenerative diseases.

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“…Other superoxide radical-generating dyes also have been used to induce AION in vivo [42, 43]. One of these, mesoporphyrin IX, has the advantage of being slowly eliminated, creating more stable blood levels and, thus, presumably allowing more time from injection to induction.…”

Section: Models Of Aaion Naion and Peaionmentioning

confidence: 99%

Ischemic optic neuropathies and their models: disease comparisons, model strengths and weaknesses

Bernstein

Miller

2015

Jpn J Ophthalmol

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Ischemic optic neuropathies (IONs) describe a group of diseases that specifically target the optic nerve and result in sudden vision loss. These include nonarteritic and arteritic anterior ischemic optic neuropathy (NAION and AAION) and posterior ischemic optic neuropathy (NPION, APION). Until recently, little was known of the mechanisms involved in ION damage, due to a lack of information about the mechanisms associated with these diseases. This review discusses the new models that closely mimic these diseases (rodent NAION, primate NAION, rodent PION). These models have enabled closer dissection of the mechanisms involved with the pathophysiology of these disorders and enable identification of relevant mechanisms and potential pathways for effective therapeutic intervention. Descriptions of the different models are included, and comparisons between the models, their relative similarities with the clinical disease, as well as differences are discussed.

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A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

Cited by 25 publications

References 50 publications

The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rNAION)

The Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rNAION)

Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells via p38 MAPK Activity

Ischemic optic neuropathies and their models: disease comparisons, model strengths and weaknesses

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