A Novel Animal Model of Partial Optic Nerve Transection Established Using an Optic Nerve Quantitative Amputator

Wang, Xu; Y, Li; He, Yan; Liang, Hongsheng; Liu, Enzhong

doi:10.1371/journal.pone.0044360

Cited by 7 publications

(8 citation statements)

References 40 publications

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“…Previously, we have only used DARC to assess complete axotomy 29 —but interestingly, in that model, we also showed peak apoptosis to occur at 7 days, suggesting a similar temporal profile and course of RGC death. Similar results were found by Wang et al 40 recently, using histological analysis in the same pONT model, with peak RGC apoptosis at 1 week which gradually decreased over 12 weeks. One study showed different results, however, which may be attributed to different experimental protocols.…”

Section: Discussionsupporting

confidence: 91%

“…One study showed different results, however, which may be attributed to different experimental protocols. First, Levkovitch-Verbin et al 13 applied a milder insult cutting the ON to a depth of 0.1 mm compared with 0.2 mm in this study and approximately 0.4 mm in the study by Wang et al 40 —we and the others have previously shown that the extent of neurotoxicity is dependent on the magnitude of the insult. 41 , 42 Second, rat species and weights were different.…”

Section: Discussionmentioning

confidence: 48%

“… 41 , 42 Second, rat species and weights were different. 31 Finally, the method used to identify apoptosis also differed: Hoechst staining in histological cross-sectional samples in the study by Levkovitch-Verbin et al , indirect estimate by Wang et al , 40 and the in vivo demonstration of annexin V-positive cells used in our study.…”

Section: Discussionmentioning

confidence: 79%

“…Sampling counting of RGCs from selected areas of the retina is therefore chosen by many researchers. 4 , 7 , 40 , 43 , 44 However, it is evident that considerable variability exists even if a significant fraction of the retinal area (quadrants or hemi-retinas) are being sampled. 30 In the present study, we have established a simple algorithm to automatically count RGCs in the entire retina and have shown that the algorithm output is comparable to manual counting.…”

Section: Discussionmentioning

confidence: 99%

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Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo

Guo¹,

Davis²,

Nizari³

et al. 2014

Cell Death Dis

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Cell-based therapies are increasingly recognized as a potential strategy to treat retinal neurodegenerative disease. Their administration, however, is normally indirect and complex, often with an inability to assess in real time their effects on cell death and their migration/integration into the host retina. In the present study, using a partial optic nerve transection (pONT) rat model, we describe a new method of Schwann cell (SC) delivery (direct application to injured optic nerve sheath, SC/DONS), which was compared with intravitreal SC delivery (SC/IVT). Both SC/DONS and SC/IVT were able to be assessed in vivo using imaging to visualize retinal ganglion cell (RGC) apoptosis and SC retinal integration. RGC death in the pONT model was best fitted to the one-phase exponential decay model. Although both SC/DONS and SC/IVT altered the temporal course of RGC degeneration in pONT, SC/DONS resulted in delayed but long-lasting effects on RGC protection, compared with SC/IVT treatment. In addition, their effects on primary and secondary degeneration, and axonal regeneration, were also investigated, by histology, whole retinal counting, and modelling of RGC loss. SC/DONS was found to significantly reduce RGC apoptosis in vivo and significantly increase RGC survival by targeting secondary rather than primary degeneration. Both SC/DONS and SC/IVT were found to promote RGC axonal regrowth after optic nerve injury, with evidence of GAP-43 expression in RGC somas and axons. SC/DONS may have the potential in the treatment of optic neuropathies, such as glaucoma. We show that SC transplantation can be monitored in real time and that the protective effects of SCs are associated with targeting secondary degeneration, with implications for translating cell-based therapies to the clinic.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo

Guo¹,

Davis²,

Nizari³

et al. 2014

Cell Death Dis

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show abstract

“…Another region of the central nervous system demonstrating variable responses to injury is the optic nerve. The optic nerve consists of axons from retinal ganglion cells, which integrate and relay visual information from the retina of the eye to visual centres in the brain (Fischer and Leibinger, 2012;Wang et al, 2012). In mammals and birds, damage to these axons can result in vision loss, as retinal ganglion cells degenerate and undergo cell death (Lang et al, 1998(Lang et al, , 2017Williams, 2017).…”

Section: Restoring the Optic Nervementioning

confidence: 99%

Tail regeneration and other phenomena of wound healing and tissue restoration in lizards

Jacyniak

McDonald

Vickaryous

2017

Journal of Experimental Biology

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Wound healing is a fundamental evolutionary adaptation with two possible outcomes: scar formation or reparative regeneration. Scars participate in re-forming the barrier with the external environment and restoring homeostasis to injured tissues, but are well understood to represent dysfunctional replacements. In contrast, reparative regeneration is a tissue-specific program that near-perfectly replicates that which was lost or damaged. Although regeneration is best known from salamanders (including newts and axolotls) and zebrafish, it is unexpectedly widespread among vertebrates. For example, mice and humans can replace their digit tips, while many lizards can spontaneously regenerate almost their entire tail. Whereas the phenomenon of lizard tail regeneration has long been recognized, many details of this process remain poorly understood. All of this is beginning to change. This Review provides a comparative perspective on mechanisms of wound healing and regeneration, with a focus on lizards as an emerging model. Not only are lizards able to regrow cartilage and the spinal cord following tail loss, some species can also regenerate tissues after full-thickness skin wounds to the body, transections of the optic nerve and even lesions to parts of the brain. Current investigations are advancing our understanding of the biological requirements for successful tissue and organ repair, with obvious implications for biomedical sciences and regenerative medicine.

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A modified chronic ocular hypertension rat model for retinal ganglion cell neuroprotection

Zhong

2013

Front. Med.

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This study aimed to modify a chronic ocular hypertension (OHT) rat model to screen for potential compounds to protect retinal ganglion cells (RGCs) from responding to increased intraocular pressure (IOP). A total of 266 rats were prepared and randomly grouped according to different time-points, namely, weeks 3, 8, 16, and 24. Rats were sedated and eye examination was performed to score as the corneal damage on a scale of 1 to 4. The OHT rat model was created via the injection of a hypertonic saline solution into the episcleral veins once weekly for two weeks. OHT was identified when the IOP at week 0 was [Symbol: see text] 6 mmHg than that at week -2 for the same eye. Viable RGCs were labeled by injecting 4% FluoroGold. Rats were sacrificed, and the eyes were enucleated and fixed. The fixed retinas were dissected to prepare flat whole-mounts. The viable RGCs were visualized and imaged. The IOP (mean ± SD) was calculated, and data were analyzed by the paired t-test and one-way ANOVA. The OHT model was created in 234 of 266 rats (87.97%), whereas 32 rats (12.03%) were removed from the study because of the absence of IOP elevation (11.28%) and/or corneal damage scores over 4 (0.75%). IOP was elevated by as much as 81.35% for 24 weeks. The average IOP was (16.68 ± 0.98) mmHg in non-OHT eyes (n = 234), but was (27.95 ± 0.97) mmHg in OHTeyes (n = 234). Viable RGCs in the OHT eyes were significantly decreased in a time-dependent manner by 29.41%, 38.24%, 55.32%, and 59.30% at weeks 3, 8, 16, and 24, respectively, as compared to viable RGCs in the non-OHT eyes (P < 0.05). The OHT model was successfully created in 88% of the rats. The IOP in the OHT eyes was elevated by approximately 81% for 24 weeks. The number of viable RGCs was decreased by 59% of the rats in a time-dependent manner. The modified OHT model may provide an effective and reliable method for screening drugs to protect RGCs from glaucoma.

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A Novel Animal Model of Partial Optic Nerve Transection Established Using an Optic Nerve Quantitative Amputator

Cited by 7 publications

References 40 publications

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo

Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo

Tail regeneration and other phenomena of wound healing and tissue restoration in lizards

A modified chronic ocular hypertension rat model for retinal ganglion cell neuroprotection

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