PolySia Nanoparticle Modulates T Cell Mediated Response as Mechanism of Action For Uveitis Treatment

Authors

Victor G. Sendra
Diyan Patel
Amit Lad
David Callanan
Tarek Hassan, Corewell Health East
Derek Kunimoto
Michael Tolentino
Anitha Krishnan

Document Type

Conference Proceeding

Publication Date

6-2025

Publication Title

Investigative Ophthalmology and Visual Science

Abstract

Purpose : Uveitis is a condition causing ocular inflammation of the uvea, comprising the iris, ciliary body, and choroids. It is primarily caused by immune T cell dysfunction associated with autoinflammation. Polysialic acid (PolySia)-nanoparticles (NPs) are glycomimetics that have shown promising therapeutic potential in vitro and in vivo mouse models of macular degeneration to dampen AMD-associated inflammation. The purpose of this study is to assess T cell response modulation to Interphotoreceptor Retinoid-Binding Protein (IRBP) antigen associated with uveitis

Methods : We analyzed the immunomodulatory effects of PolySia-NPs in the T helper response (Th1, Th2 and Treg) to IRBP. Human PBMCs were incubated with IRBP in Th1/Th17 polarizing conditions in presence of PolySia-NPs and sucrose as control. T cell response was analyzed after re-stimulation with IRBP. IFN-γ, IL-17, IL-10 and TNF-α cytokine production from supernatant were quantified by multiplexing ELISA assays. CD69 activation marker and FoxP3, T-bet (Treg and Th1 transcription factors) were analyzed by flow cytometry on CD4+ T cells.

Results : After re-stimulation with IRBP, human PBMC supernatants showed a significant decrease in proinflammatory cytokines IFN-γ, IL-17, and TNF-α, and a significant increase in anti-inflammatory IL-10 in the presence of PolySia-NPs compared to the sucrose control. Flow cytometry analysis revealed a significant increase in CD25+ FoxP3+ Tregs with PolySia-NPs compared to the sucrose control, while no changes were observed in T-bet transcription factor expression or T cell activation

Conclusions : Polysialic acid (PolySia)-nanoparticles (NPs), which selectively target Siglec, significantly suppress Th1 and Th17 responses to IRBP by reducing pro-inflammatory cytokine production and increasing regulatory T cells (Tregs) with increased IL-10. Our in vitro data strongly supports the potential use of PolySia-NPs as a T cell immunomodulator for uveitis treatment

Volume

66

Issue

8

First Page

657

Comments

Association for Research in Vision and Ophthalmology ARVO Annual Meeting, May 4-8, 2025, Salt Lake City, UT

Last Page

657

Recommended Citation

Sendra VG, Patel D, Lad A, Callanan D, Hassan T, Kunimoto D, et al. PolySia nanoparticle modulates T cell mediated response as mechanism of action for uveitis treatment. Invest Ophthal Vis Sci. 2025 Jun;66(8):657.