Conedera, Federica M; Runnels, Judith M; Stein, Jens V; Alt, Clemens; Enzmann, Volker; Lin, Charles P (2023). Assessing the role of T cells in response to retinal injury to uncover new therapeutic targets for the treatment of retinal degeneration. Journal of neuroinflammation, 20(1), p. 206. BioMed Central 10.1186/s12974-023-02867-x
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BACKGROUND
Retinal degeneration is a disease affecting the eye, which is an immune-privileged site because of its anatomical and physiological properties. Alterations in retinal homeostasis-because of injury, disease, or aging-initiate inflammatory cascades, where peripheral leukocytes (PL) infiltrate the parenchyma, leading to retinal degeneration. So far, research on PL's role in retinal degeneration was limited to observing a few cell types at specific times or sectioning the tissue. This restricted our understanding of immune cell interactions and response duration.
METHODS
In vivo microscopy in preclinical mouse models can overcome these limitations enabling the spatio-temporal characterization of PL dynamics. Through in vivo imaging, we assessed structural and fluorescence changes in response to a focal injury at a defined location over time. We also utilized minimally invasive techniques, pharmacological interventions, and knockout (KO) mice to determine the role of PL in local inflammation. Furthermore, we investigated PL abundance and localization during retinal degeneration in human eyes by histological analysis to assess to which extent our preclinical study translates to human retinal degeneration.
RESULTS
We demonstrate that PL, especially T cells, play a detrimental role during retinal injury response. In mice, we observed the recruitment of helper and cytotoxic T cells in the parenchyma post-injury, and T cells also resided in the macula and peripheral retina in pathological conditions in humans. Additionally, we found that the pharmacological PL reduction and genetic depletion of T-cells reduced injured areas in murine retinas and rescued the blood-retina barrier (BRB) integrity. Both conditions promoted morphological changes of Cx3cr1+ cells, including microglial cells, toward an amoeboid phenotype during injury response. Interestingly, selective depletion of CD8+ T cells accelerated recovery of the BRB compared to broader depletions. After anti-CD8 treatment, the retinal function improved, concomitant to a beneficial immune response.
CONCLUSIONS
Our data provide novel insights into the adaptive immune response to retinal injury in mice and human retinal degeneration. Such information is fundamental to understanding retinal disorders and developing therapeutics to modulate immune responses to retinal degeneration safely.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde 04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology |
UniBE Contributor: |
Conedera, Federica Maria, Enzmann, Volker |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1742-2094 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Sep 2023 15:14 |
Last Modified: |
29 Oct 2023 02:23 |
Publisher DOI: |
10.1186/s12974-023-02867-x |
PubMed ID: |
37689689 |
Uncontrolled Keywords: |
Adaptive immune cells CD8+ T cells Human In vivo imaging Microglia Mouse Retinal laser-injury |
BORIS DOI: |
10.48350/186205 |
URI: |
https://boris.unibe.ch/id/eprint/186205 |
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