# In vivo modeling of autoantibody-induced optic neuritis

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2022 · $171,564

## Abstract

Project Summary
 Vision loss from optic neuritis (ON) is a frequent consequence of autoimmune-mediated central nervous
system (CNS) disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and
myelin oligodendrocyte glycoprotein associated disease (MOGAD). The severity of vision loss, prognosis for
recovery, response to therapy, and risk of recurrence varies significantly between disorders; however, our
understanding of the pathophysiologic mechanisms driving these differences remain unclear. Reliable animal
models that faithfully reproduce human MS-, NMOSD-, and MOGAD-specific pathology of the visual system are
desperately needed to advance our understanding of disease pathobiology and advance treatment.
 MS, NMOSD, and MOGAD are differentiated by the production of disease-specific pathogenic
autoantibodies. We hypothesize that these disease-specific autoantibodies initiate distinctive patterns of
inflammatory optic nerve injury that clinically distinguish ON in MS, MNOSD and MOGAD. We intend to develop
novel models of MS, NMOSD, and MOGAD ON by delivering disease-specific monoclonal recombinant
antibodies (rAbs) or serum IgG into the rat retrobulbar space using a novel surgical technique. Our long-term
goal is to generate transformative in vivo models of disease-specific antibody-mediated optic neuritis to advance
translational research.
 In specific aim 1, we will measure the time course of functional impairment and inflammatory injury during
the acute phase of autoantibody-driven optic neuritis. We will measure the anatomic and functional
consequences of autoantibody-mediated optic neuritis in vivo using an array of tools that assess visual acuity,
retinal structure, and electrophysiology. We will correlate our in vivo results to immunohistopathologic
evaluations of complement deposition, myelin loss, and inflammatory cell infiltration in optic nerve tissue.
 In specific aim 2, we will quantify visual recovery and remyelination following autoantibody-driven optic
neuritis. We will compare visual recovery and tissue repair in untreated and corticosteroid-treated animals using
functional and structural measurements. These studies will further validate disease-specificity by comparing
recovery in our animal ON models to those observed in their human counterparts. In vivo metrics will be
correlated with measures of tissue pathology, remyelination, and axonal injury.
 The development and validation of these novel disease-specific models of ON will significantly advance our
understanding of MS, NMOSD, and MOGAD ON pathobiology and provide an invaluable resource for future
translational and therapeutic studies.

## Key facts

- **NIH application ID:** 10429925
- **Project number:** 5R21EY032399-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Jeffrey L Bennett
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $171,564
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429925

## Citation

> US National Institutes of Health, RePORTER application 10429925, In vivo modeling of autoantibody-induced optic neuritis (5R21EY032399-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10429925. Licensed CC0.

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