In vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis

Zhang, Yikui; Zhang, Si; Xia, Yu; Ji, Yuanfei; Jiang, Wenhao; Li, Mengyun; Huang, Haoliang; Xu, Mingna; Sun, Jiaying; Ye, Qian; Hu, Yang; Wu, Wencan

doi:10.1016/j.exer.2020.108117

Cited by 15 publications

(28 citation statements)

References 47 publications

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“…RGC density in the contralateral eyes remained stable at 1 and 3 mpi (Supplementary Figure 2B, left panel). It is worth noticing that our previous study in goat showed that retrobulbar ON crush resulted in more severe RGC loss at 3 mpi (less than 5% survival) 24 .…”

Section: Progressive Rgc and On Degeneration In Goat Ton Modelmentioning

confidence: 88%

“…The PVEP, which is more reproducible than FVEP in human 19 , can be elicited in rhesus macaques according to our previous study 24 . Therefore, we replaced the FVEP test with the PVEP test in rhesus macaques.…”

Section: Flash Visual Evoked Potential (Fvep)mentioning

confidence: 99%

“…PERG is the retinal electrical signal activated by patterned visual stimuli, the amplitude of which indicates the functional integrity of RGCs 20 . PERG recording in goats and rhesus macaques has been previously reported 24 . Briefly, the goat was anesthetized with xylazine.…”

Section: Pattern Electroretinogram (Perg) Recordingsmentioning

confidence: 99%

“…Direct PLR (dPLR) is the PLR in the ipsilateral eye while indirect PLR (iPLR) occurs in the contralateral eye. This method has been previously described 24 . Briefly, the goat was dark-adapted for 5 minutes after anesthesia with xylazine.…”

Section: Pupillary Light Response (Plr) Testmentioning

confidence: 99%

“…Retinal OCT imaging was used to measure the thickness of the retinal ganglion cell complex including the RNFL, RGC and IPL layers, which represent the RGC axons, somas and dendrites, respectively. This method has been previously described 24 . Briefly, after anesthesia, the OCT images were taken with peripapillary circular scan pattern (Heidelberg Spectralis OCT system, Germany).…”

Section: Spectral-domain Optical Coherence Tomography (Sd-oct) Imagingmentioning

confidence: 99%

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Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy

Zhang

et al. 2021

Preprint

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Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: 1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. 2) Even with possible access for “local refrigeration”, cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4°C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with hibernation-mimicking cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.

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Section: Progressive Rgc and On Degeneration In Goat Ton Modelmentioning

confidence: 88%

Section: Flash Visual Evoked Potential (Fvep)mentioning

confidence: 99%

Section: Pattern Electroretinogram (Perg) Recordingsmentioning

confidence: 99%

Section: Pupillary Light Response (Plr) Testmentioning

confidence: 99%

Section: Spectral-domain Optical Coherence Tomography (Sd-oct) Imagingmentioning

confidence: 99%

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