Regulatory T cells limit age-associated retinal inflammation and neurodegeneration

María Llorián-Salvador, Alerie G. de Fuente*, Christopher E. McMurran, Amy Dashwood, James Dooley, Adrian Liston, Rosana Penalva, Yvonne Dombrowski, Alan W. Stitt*, Denise C. Fitzgerald

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Background
Ageing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown.

Methods
Regulatory T cells were selectively depleted in both young (2–4 months) and aged (18–23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni’s post hoc test.

Results
Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes.

Conclusion
Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.

Original languageEnglish
Article number32
Number of pages17
JournalMolecular Neurodegeneration
Volume19
DOIs
Publication statusPublished - 05 Apr 2024

Bibliographical note

© 2024. The Author(s).

Keywords

  • Mice
  • Animals
  • T-Lymphocytes, Regulatory
  • Gliosis
  • Retina
  • Macular Degeneration
  • Inflammation

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