Comparison of different optomotor response readouts for visual testing in experimental autoimmune encephalomyelitis-optic neuritis

Abstract

Optomotor response is increasingly used in preclinical research for evaluating the visual function in rodents. However, the most suitable measuring protocol for specific scientific questions is not always established. We aimed to determine the optimal parameters for visual function analysis in experimental autoimmune encephalomyelitis optic neuritis (EAEON), an animal model for multiple sclerosis. Contrast sensitivity as well as spatial frequency both had a low variance and a good test-retest reliability. Also, both parameters were able to differentiate between the EAEON and the control group. Correlations with the retinal degeneration, assessed by optical coherence tomography, the infiltration of immune cells, and the clinical disability score revealed that spatial frequency was superior to contrast sensitivity analysis. We therefore conclude that spatial frequency testing is better suited as visual acuity assessment in C57Bl/6 J EAEON mice. Furthermore, contrast sensitivity measurements are more time consuming, possibly leading to more stress for the animals.

Distinctive waves of innate immune response in the retina in experimental autoimmune encephalomyelitis

“…Thus, in vivo CSLO measurements are reliable for longitudinal analysis of morphological changes in CX3CR1 GFP/+ retinae. This is the first study to our knowledge employing CSLO for in vivo immune cell imaging in a MS mouse model validating CSLO as a feasible and reliable technique for the longitudinal analysis of retinal immune cell dynamics in mice (44)(45)(46), CSLO empowers the afferent visual system in rodents as a comprehensive model to study the pathophysiology of CNS inflammation (42).…”

“…This is the first study to our knowledge employing CSLO for in vivo immune cell imaging in a MS mouse model validating CSLO as a feasible and reliable technique for the longitudinal analysis of retinal immune cell dynamics in mice expressing fluorescent proteins. Especially in combination with other advanced techniques such as OCT and objective functional measurements ( 44 – 46 ), CSLO empowers the afferent visual system in rodents as a comprehensive model to study the pathophysiology of CNS inflammation ( 42 ).…”

Semi-Automated Live Tracking of Microglial Activation in CX3CR1GFP Mice During Experimental Autoimmune Encephalomyelitis by Confocal Scanning Laser Ophthalmoscopy

“…The third group consisted of untreated CX3CR1 GFP mice (naïve group). To rate the EAE severity of the mice, we determined the clinical EAE score daily using the following criteria: (0) no disease; (0.5) mild tail paresis; (1) obvious tail paresis or plegia; (1.5) tail plegia and no righting reflex; (2) mild signs of hind limb paresis with clumsy gait; (2.5) obvious signs of hind limb paresis; (3) hind limb plegia, mouse drags one leg behind; (3.5) hind limb plegia, mouse drags both legs behind; (4) mild signs of quadriparesis; (4.5) quadriplegia; and (5) death or moribund ( 23 , 24 ).…”

“…OCT methodology is reported according to the updated APOSTEL recommendations ( 27 , 28 ). Like in previous OCT studies ( 23 , 24 , 29 , 30 ), we performed volume scans (25 x 25°) to determine retinal layer thicknesses using a Spectralis™ HRA+OCT device (Heidelberg Engineering, Germany) under ambient light conditions and excluded images with a quality below 20 decibels. We determined the thickness of the total retinal layer thickness (TRT) and of the inner retinal layer (IRL), which is composed of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL), using the automatic segmentation of the Heidelberg Eye Explorer™ software (version 1.9.10.0).…”

“…Eye drops with phenylephrine (2.5%)-tropicamide (0.5%) were administered to dilate the mouse pupils and were replaced after approximately one minute by Visc-Ophtal eye gel (Dr. Winzer, Berlin, Germany) to prevent corneal desiccation. Finally, we applied a custom-made contact lens (+4 diopters) to the eye before OCT and cSLO measurement for better image resolution as previously described (24)(25)(26).…”