Retinal pathology in spontaneous opticospinal experimental autoimmune encephalitis mice

Area of Science:

• Neuroscience
• Immunology
• Ophthalmology

Background:

• Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) leads to optic nerve inflammation and retinal ganglion cell (RGC) loss.
• The mechanisms underlying RGC injury in MOGAD are not fully understood.
• Existing models of experimental autoimmune encephalomyelitis (EAE) have not fully characterized retinal pathology.

Purpose of the Study:

• To characterize the retinal pathology in the double transgenic opticospinal EAE (OSE) mouse model of MOGAD.
• To assess RGC loss and optic nerve inflammation in OSE mice.
• To evaluate the OSE model's utility for studying MOGAD and testing neuroprotective agents.

Main Methods:

• Utilized the double transgenic opticospinal EAE (OSE) mouse model, which spontaneously develops MOG35-55 peptide-specific T and B cell responses.
• Assessed optic nerve inflammation, reactive astrogliosis, and RGC counts in OSE mice at 8 and 10 weeks of age.
• Compared RGC counts in OSE mice to age-matched wild-type controls.

Main Results:

• OSE mice at 8 weeks exhibited optic nerve inflammation, reactive astrogliosis, and RGC loss.
• By 10 weeks, OSE mice showed a 50% reduction in RGCs compared to wild-type controls.
• The observed retinal pathology in OSE mice closely resembles human optic neuritis.

Conclusions:

• The OSE mouse model spontaneously develops optic neuritis and significant RGC loss, mirroring human MOGAD.
• This model is suitable for investigating the mechanisms of RGC injury in MOGAD.
• The OSE model can serve as a valuable platform for screening neuroprotective compounds for MOGAD and related optic neuropathies.