June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Increased T-regulatory cell activity protects retinal ganglion cells in glaucoma
Author Affiliations & Notes
  • Huilan zeng
    Ophthalmology, The University of Iowa, Iowa City, Iowa, United States
    Ophthalmology, the Department of Veterans Affairs, Iowa City, Iowa, United States
  • Markus H Kuehn
    Ophthalmology, The University of Iowa, Iowa City, Iowa, United States
    Ophthalmology, the Department of Veterans Affairs, Iowa City, Iowa, United States
  • Footnotes
    Commercial Relationships   Huilan zeng None; Markus Kuehn None
  • Footnotes
    Support  VA IOR RX002860
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3922. doi:
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      Huilan zeng, Markus H Kuehn; Increased T-regulatory cell activity protects retinal ganglion cells in glaucoma. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3922.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Our previous studies have shown that experimental glaucoma in mice activates T cell-driven autoimmune response that can further contribute to vision loss. Regulatory T cells (Tregs) are a specialized subset of T cells that suppress immune responses, thereby maintaining homeostasis and self-tolerance. Here, we sought to explore whether induction of increased T-regulatory cell (T-reg) activity ameliorates vision loss in mice with glaucoma.

Methods : Lymphocyte activation gene 3 (Lag3), also known as CD223, negatively regulates T cell activation, proliferation, and cytokine production. We induced ocular hypertension (OHT) in Lag3fl/fl.Foxp3CreERT2-GFP mice to establish a chronic glaucoma model. Intraperitoneal injection of tamoxifen was used to conditionally remove the Lag3 gene Treg cells of adult mice to increase their abundance and activity. Mice were divided into 5 groups: naïve (n=10), tamoxifen without OHT (n=7), Untreated (OHT without tamoxifen, n=8), Prevention (tamoxifen before OHT, n=9) and Treatment (tamoxifen after OHT, n=10). Visual function was assessed monthly by optokinetic response testing. 12 weeks after OHT induction, optic nerve damage was determined by p-phenylenediamine (PPD) staining.

Results : Tamoxifen injection increased the proportion of CD4+ Treg cells detected in peripheral lymph nodes (naïve vs tamoxifen injected, 14.6%vs18.8%, p=0.0287) and the spleen (naïve vs tamoxifen injected, 10.8%vs15.5%, p=0.0043). 12 weeks after induction of OHT, mice in the Treatment group showed higher visual function when compared to those in the Untreated group (0.366 c/d vs. 0.322 c/d, p=0.027). However, mice in the Prevention group did not perform significantly better than those in the Untreated group (0.336 c/d, p=0.89). Histologically, significantly fewer damaged axons were observed in the optic nerves of the Treatment group when compared to the Untreated group (9.1±6.2 vs. 20.4±14.2, p=0.036). Animals in the Prevention group displayed slightly less damage than untreated mice, but statistical significance was not reached (13.4±5.4, p=0.3532).

Conclusions : These results demonstrate that increasing Treg cell activity can reduce experimental glaucoma damage in mice. Our findings suggest that immunomodulatory therapy aimed to minimize the impact of T-cell mediated damage in glaucoma may be beneficial for some patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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