The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina

Yoshimoto, Takuya; Chaya, Taro; Varner, Leah R.; Ando, Makoto; Tsujii, Toshinori; Motooka, Daisuke; Kimura, Kazuhiro; Furukawa, Takahisa

doi:10.1016/j.jbc.2023.105461

Cited by 2 publications

(1 citation statement)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, microglia release cytokines that attract T-cells to the retinal parenchyma, thereby contributing to immune responses in retinal degenerative diseases (Ramirez et al, 2017). Müller cells span the entire depth of the retina, contributing to light transmission and maintaining homeostasis under physiological conditions (Szabó et al, 2022; Yoshimoto et al, 2023). In response to retinal degeneration, they exhibit reactivity to protect the retina from further damage and promote repair following pathological insult.…”

Section: Introductionmentioning

confidence: 99%

Glia-Mediated Antigen Presentation In The Retina During Degeneration

Intonti,

Kokona,

Zinkernagel

et al. 2024

Preprint

View full text Add to dashboard Cite

Glia antigen-presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. The intricate mechanisms underlying their local coordination and activation remain unclear. Our study integrates an animal model of retinal injury, retrospective analysis of human retinas, and in vitro experiments to elucidate insights into the pivotal role of antigen presentation in neuroimmunology during retinal degeneration, uncovering the involvement of various glial cells, notably Muller glia, and microglia. Glial cells act as sentinels, detecting antigens released during degeneration and interacting with T-cells via MHC molecules, which are essential for immune responses. Microglia function as APCs via the MHC class II pathway, upregulating key molecules such as Csf1r and cytokines. In contrast, Muller cells act as atypical APCs through the MHC class I pathway, exhibiting upregulated antigen processing genes and promoting a CD8+ T-cell response. Human retinal specimens corroborate these findings, demonstrating glial activation and MHC expression correlating with degenerative changes. In vitro assays also confirmed differential T-cell migration responses to activated microglia and Muller cells, highlighting their role in shaping the immune milieu within the retina. These insights emphasize the complex interplay between glial cells and T-cells, influencing the inflammatory environment and potentially modulating degenerative processes. In summary, our study emphasizes the involvement of retinal glial cells in modulating the immune response after insults to the retinal parenchyma. Thus, unraveling the intricacies of glia-mediated antigen presentation in retinal degeneration is essential for developing precise therapeutic interventions for retinal pathologies.

show abstract

Section: Introductionmentioning

confidence: 99%