![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
Preview |
PDF (Supplementary Material)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
| Item Type: | Article |
|---|---|
| Title: | Multimodal longitudinal optical imaging reveals optic neuritis preceding retinal pathology in experimental autoimmune encephalomyelitis |
| Creators Name: | Raspe, R., Günther, R., Uecker, R., Rakhymzhan, A., Paul, F., Radbruch, H., Niesner, R.A. and Hauser, A.E. |
| Abstract: | BACKGROUND AND OBJECTIVES: Inflammatory demyelinating diseases of the CNS, chief among them multiple sclerosis (MS), are a major cause of disability in young adults. Early manifestations of MS commonly involve visual dysfunction, which is often caused by optic neuritis and is accompanied by quantifiable structural changes of the anterior visual pathway. Retinal optical coherence tomography (OCT) has emerged as an important tool for clinical assessment of these structural alterations, but the underlying pathobiological mechanisms and temporal dynamics are yet poorly understood at a cellular level. METHODS: Using the experimental autoimmune encephalomyelitis (EAE) model of MS in fluorescent reporter mouse strains for neuronal function and innate immune cells, we use a unique combination of retinal intravital 2-photon microscopy (2PM) and OCT. In this fashion, we elucidate the spatiotemporal interplay of functional and structural retinal changes over the course of 1 month after EAE induction, with histopathologic imaging validating main results. RESULTS: While all mice display histologic signs of optic neuritis early after EAE induction and independently of motor symptom severity, retinal signs of neuronal stress and parenchymal immune activation spike well after clinical peak of disease, with no signs of lasting structural damage appearing within 1 month after EAE induction. Thus, local retinal endpoints appear to be functions of downstream axonal damage rather than of immediate immune activation directed at the retina. However, as early as 1 week after EAE induction, retinal 2PM can detect recruitment of perivascular immune cells towards the optic nerve (ON), providing the earliest sign of disease activity in otherwise clinically inconspicuous mice. DISCUSSION: Our work identifies the recruitment of CX3CR1+ cells to the ON as an early sign of disease underlining the importance of combined structural and functional retinal imaging for the spatiotemporal characterization of neuroinflammatory and neurodegenerative processes. It further proposes retinal phagocyte orientation, morphology, and abundance as potential surrogate markers for neurodegenerative activity. |
| Keywords: | Experimental Autoimmune Encephalomyelitis, Inbred C57BL Mice, Multimodal Imaging, Optic Neuritis, Optical Coherence Tomography, Retina, Transgenic Mice, Animals, Mice |
| Source: | Neurology Neuroimmunology & Neuroinflammation |
| ISSN: | 2332-7812 |
| Publisher: | American Academy of Neurology |
| Volume: | 12 |
| Number: | 1 |
| Page Range: | e200338 |
| Date: | January 2025 |
| Official Publication: | https://doi.org/10.1212/NXI.0000000000200338 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
