研究目的
Investigating whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration.
研究成果
The loss of optic nerve axons demonstrated in the shp model resulted in moderate thinning of the RNFL confirmed by OCT and histology. These results indicate that OCT-derived RNFL measurement can be a useful surrogate biomarker of optic nerve axon loss and potentially disease progression in demyelinating diseases.
研究不足
The study was not designed to determine whether there was progressive RNFL thinning in the shp dogs as that would require further longitudinal observations on more animals. The lack of a decrease in the RGC numbers observed might be due to retinal tissue sampling restrictions and to differences in the topographic distribution of RGCs in the dog retina.
1：Experimental Design and Method Selection:
The study used an animal model of Pelizaeus-Merzbacher disease (shp) to perform bilateral longitudinal measurements of the peripapillary RNFL using spectral-domain OCT, electroretinograms (ERG), and visual evoked potentials (VEP) in affected and control animals from 5 months to 2 years and in individual animals at single time points. Light and electron microscopy of the optic nerve and retina and histomorphometric measurements of the RNFL were compared to OCT data.
2：Sample Selection and Data Sources:
Affected male dogs and female carriers were identified by PCR of genomic DNA isolated from whole blood. All animals were handled and treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
3：List of Experimental Equipment and Materials:
Optical coherence tomography was performed using a Cirrus SD-OCT (Software version 5.9.1.096; Carl Zeiss Meditec, Dublin, CA, USA). Electroretinograms and VEPs were recorded with a GoldLens contact lens electrode and VEPs with subdermal electrodes using an Espion 2 Color-burst system (Diagnosis, LLC, Loewell, MA, USA).
4：096; Carl Zeiss Meditec, Dublin, CA, USA). Electroretinograms and VEPs were recorded with a GoldLens contact lens electrode and VEPs with subdermal electrodes using an Espion 2 Color-burst system (Diagnosis, LLC, Loewell, MA, USA).
Experimental Procedures and Operational Workflow:
4. Experimental Procedures and Operational Workflow: All dogs were premedicated with dexmedetomidine, anesthetized with isoflurane, and ventilated under the care of a veterinary anesthesiologist. Pupils were dilated with phenylephrine 1% and tropicamide 2.5% drops. Optical coherence tomography was performed using a Cirrus SD-OCT.
5：5% drops. Optical coherence tomography was performed using a Cirrus SD-OCT.
Data Analysis Methods:
5. Data Analysis Methods: A Pearson product-moment correlation coefficient was computed to assess the relationship between the OCT RNFL thickness, histologic RNFL thickness and percentage of axonal area in the retina. Two-tailed Student's t-tests were performed to compare histologic RNFL thickness, RGCs density, retinal total axonal area, retinal percentage of axonal area, and distribution of retinal axonal diameter between control and affected animals at the same time points.
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