T cell-mediated ocular autoimmunity

by Soghra Kargaran
Doctoral thesis
Date of Examination:2024-11-11
Date of issue:2025-03-07
Advisor:Prof. Dr. Alexander Flügel
Referee:Prof. Dr. Christine Stadelmann-Nessler
Referee:Prof. Dr. André Fischer
Referee:Prof. Dr. Martin Weber
Referee:Prof. Dr. Lutz Walter
Referee:Prof. Dr. Holger Reichardt
Persistent Address: http://dx.doi.org/10.53846/goediss-11134

 

 

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Abstract

English

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS), leading to inflammatory lesions in the brain and spinal cord. The autoimmune process can affect both the gray and white matter. Retina and optic nerve, as part of the CNS, are frequently involved in the inflammatory processes. This leads to degenerative damage to both the retina and optic nerve, leading to permanent vision impairment. The development of autoimmune inflammation in the eye and its effects on the ocular system, particularly concerning how inflammation in white or gray matter tissue impacts the eye, remains poorly understood. In this study we established an intravital Two-photon laser scanning microscopy (TPLSM) setup to monitor in real time how the autoimmune process unfolds in the retina. This approach was then applied to models of T-cell-mediated autoimmunity targeting white matter and gray matter, induced by the transfer of myelin-reactive or neuronal-reactive T cells, respectively. We observed that, regardless of antigen specificity, both myelin-reactive and neuronal-reactive T cells were able to enter the retina. However, they exhibited fundamentally different motility behaviors, entry points, and lesion distributions. A detailed analysis of the gray matter autoimmunity model revealed that neuronal-reactive T cells, upon entering the retina, encountered their cognate antigen and were locally reactivated. This reactivation led to acute inflammation and subsequent chronic damage in the retinal tissue. The structural changes were not confined to the retina but also extended to the optic nerve. These findings suggest that primary T-cell-mediated neurodegeneration in the retina can occur independently of initial optic nerve inflammation and may contribute to secondary optic nerve pathology. Further studies are needed to elucidate the mechanisms of damage in both gray and white matter autoimmunity.
Keywords: Eye, EAE; Autoimmunity, Multiple Sclerosis