In vivo detection of experimental optic neuritis by pupillometry

Abstract

Optic neuritis is an inflammatory demyelination of optic nerve often occurring in multiple sclerosis (MS) patients. Mice with experimental autoimmune encephalomyelitis (EAE), an MS model, develop optic neuritis, but it is detected histologically after sacrifice, limiting the ability to monitor progression or treatment in vivo. We examined whether pupillary light responses measured by pupillometry can identify eyes with optic neuritis in EAE mice. C57BL/6 mice were exposed to unilateral light flashes of increasing intensity at 10 second intervals (4.7, 37, and 300 μW/cm2). Pupillary responses were recorded with a commercially available pupillometer. EAE was then induced by immunization with myelin oligodendrocyte glycoprotein. Pupillometry was repeated up to 17 days post-immunization, and responses were correlated with optic nerve inflammation. By day 17 post-immunization, 90% of EAE eyes had optic nerve inflammation. EAE eyes had significantly reduced pupillary constriction compared to control eyes. Mice exhibited more than a 25% decrease in pupillary constriction in at least one eye by days 13-15 post-immunization. In some eyes, pupil responses decreased prior to onset of detectable inflammation. Results show that pupillometry detects decreased optic nerve function in experimental optic neuritis, even in the absence of histological detection. Measuring pupillary constriction allows in vivo identification and functional assessment of eyes with optic neuritis that will be useful in evaluating potential therapies over time. Furthermore, results demonstrate that decreased visual function occurs early in optic neuritis, before optic nerve inflammation reaches its peak level.

Overexpression of SIRT1 Protein in Neurons Protects against Experimental Autoimmune Encephalomyelitis through Activation of Multiple SIRT1 Targets

“…In this study, we show that SIRT1 overexpression actively attenuates the symptoms of disease progression in EAE. The SIRT1 activator resveratrol (SRT501) was shown to suppress EAE, exhibiting protection against myelin breakdown in the EAE animal model (26)(27)(28). Our present observations provide further evidence supporting the beneficial effects of SIRT1 on myelin-forming OLs in EAE spinal cord.…”

“…SIRT1 has been linked to neurodegenerative diseases (23)(24)(25). A pharmaceutical formulation of resveratrol (SRT501) that activates SIRT1 prevents neuronal damage and long-term neurologic dysfunction in EAE (26)(27)(28). Importantly, either SRT501 or other SIRT1-activating compounds regulate inflammation in EAE (26)(27)(28).…”

“…A pharmaceutical formulation of resveratrol (SRT501) that activates SIRT1 prevents neuronal damage and long-term neurologic dysfunction in EAE (26)(27)(28). Importantly, either SRT501 or other SIRT1-activating compounds regulate inflammation in EAE (26)(27)(28). This result suggests that resveratrol has the potential to complement current immunomodulatory MS therapies that fail to prevent neurodegeneration.…”

Inflammatory demyelination induces glia alterations and ganglion cell loss in the retina of an experimental autoimmune encephalomyelitis model

“…We immunized C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG 35–55 ), a widely applied method to induce EAE in animals [1,5,12,13]. Both MS and EAE are characterized by inflammation and neurodegeneration in the spinal cord and the brain [12].…”

Clinical Utility of an Automated Pupillometer in Patients with Acute Brain Lesion

“…Meeker et al 12) reported that inter-examiner disagreement regarding the pupillary reaction was 39% for manual examinations compared with 1% for automated pupillometers. Hence, studies to define the relationship between clinical manifestations and PLR determined by automated pupillometer have been conducted in various fields 1 2 5 6 7 9 15 17 18) .…”