in-vivo-methods-to-assess-retinal-ganglion-cell-optic-nerve-function

<em>In Vivo</em> Methods to Assess Retinal Ganglion Cell and Optic Nerve Function and Structure in Large Animals

The optic nerve collects axons signals from the retinal ganglion cells and transmits visual signal to the brain. Large animal models of optic nerve injury ...

Wenzhou Medical University

Large animal models of optic nerve injury are essential for translating novel findings into effective therapies due to their similarity to humans in many respects. However, most current tests evaluating the integrity of retinal ganglion cells (RGCs) and optic nerve (ON) are based on rodent animal models. We aimed to evaluate and optimize the in vivo methods to assess RGCs and ON's function and structure in large animals in terms of reproducibility, simplicity and sensitivity. Both goats and rhesus macaques were employed in this study. By using goats, we found anesthesia with isoflurane or xylazine resulted in different effects on reproducibility of flash visual evoked potential (FVEP) and pattern electroretinogram (PERG). FVEP with the large-Ganzfeld stimulator was significantly more stable than that with mini-Ganzfeld stimulator. PERG with simultaneous binocular stimulation, with superior simplicity over separate monocular stimulation, was appliable in goats due to undetectable interocular crosstalk of PERG signals. After ON crush in goats, some FVEP components, PERG, OCT and PLR demonstrated significant changes, in line with the histological study. By using rhesus macaque, we found the implicit time of PVEP, FVEP and PERG were significantly more reproducible than amplitudes, and OCT and PLR demonstrated small intersession variation. In summary, we established an optimized system to evaluate integrity of RGCs and ON in large animals in vivo, facilitating usage of large animal models of optic nerve diseases.

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

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

In vivo evaluation of outer retinal function and structure after retrobulbar optic nerve crush by lateral orbitotomy in goats.

An implantation cyst after orbital wall reconstruction may present as a late complication, which can cause local pain, proptosis, diplopia, and vision impairment. Previous surgical strategies prefer transconjunctival or subtarsal approach for cyst drainage, a similar approach to orbital wall reconstruction. These strategies may have risk of secondary infection. Herein, we propose an endoscopic transnasal surgical approach, through which the removal of implant and cyst drainage can be performed conveniently. The residual, medial single-layer cyst wall is generally strong enough to support the orbital soft tissues without the need for a new implant. We believe this surgical approach can simplify the procedure, reduce the complications, and prevent cyst recurrence.

Article	Year
In vivo evaluation of retinal ganglion cells and optic nerve's integrity in large animals by multi-modality analysis. Experimental eye research\| PubMed ID: 32598972	2020
In vivo evaluation of outer retinal function and structure after retrobulbar optic nerve crush by lateral orbitotomy in goats. Experimental eye research\| PubMed ID: 34097904	2021
Endoscopic transnasal drainage for orbital implantation cyst after orbital wall reconstruction. Indian journal of ophthalmology\| PubMed ID: 34146062	2021

Jiaying Sun

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