Jana Koch, Dennis-Dominik Rosmus, Annika Hausmann, Aude Chiot, Franz Arnold, Takahiro Masuda, Katrin Kierdorf, Stefanie Marie Hansen, Heidrun Kuhrt, Janine Fröba, Julian Wolf, Stefaniya Boneva, Martin Gericke, Bahareh Ajami, Marco Prinz, Clemens Lange, Peter Wieghofer
- Introduction: Hyalocytes are tissue resident macrophages of the vitreous body of the eye. They are involved in multiple vitreoretinal diseases with a large impact on society such as diabetic retinopathy. However, their ontogeny and fate are still largely unknown. The aim of this study was to characterize hyalocytes in comparison to other macrophages focusing on their marker profile, their embryonic origin and turnover during homeostasis.
Methods: Transgenic reporter mice, fate mapping and parabiosis experiments were combined with immunofluorescent imaging to study these cells in the eye.
Results: We identified a distinct signature of hyalocytes as CX3CR1+IBA1+F4/80+CD163+CD206+LYVE1+MHCII-HEXB-TMEM119- cells separating them clearly from retinal microglia. Furthermore, murine hyalocytes originate from the yolk sac and seed the developing eye prenatally, like microglia. In sharp contrast to the existing body of literature, they don’t show a contribution of blood-derived monocytes underIntroduction: Hyalocytes are tissue resident macrophages of the vitreous body of the eye. They are involved in multiple vitreoretinal diseases with a large impact on society such as diabetic retinopathy. However, their ontogeny and fate are still largely unknown. The aim of this study was to characterize hyalocytes in comparison to other macrophages focusing on their marker profile, their embryonic origin and turnover during homeostasis.
Methods: Transgenic reporter mice, fate mapping and parabiosis experiments were combined with immunofluorescent imaging to study these cells in the eye.
Results: We identified a distinct signature of hyalocytes as CX3CR1+IBA1+F4/80+CD163+CD206+LYVE1+MHCII-HEXB-TMEM119- cells separating them clearly from retinal microglia. Furthermore, murine hyalocytes originate from the yolk sac and seed the developing eye prenatally, like microglia. In sharp contrast to the existing body of literature, they don’t show a contribution of blood-derived monocytes under homeostatic conditions but are a long-lived self-maintaining population.
Discussion: Our study is the first to show a yolk sac-derived origin of hyalocytes while excluding a long-thought contribution of peripheral blood monocytes with several transgenic mouse lines and models. Our findings not only clarify the source of hyalocytes but also provide an important resource for future studies of hyalocytes in terms of marker selection, in line with previous eye macrophage studies. Importantly, the senescence of hyalocytes as a long-lived, self-maintaining cell population, might be contributing directly to the development of vitreoretinal diseases. This insight provides a better understanding of disease mechanisms and with this, new therapeutic avenues for patient treatment in the future.…
