Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body

The purpose of this paper is to explore the developmental origin, biological characteristics, and association with eye diseases of tissue-resident macrophages in the field of ophthalmology—hyalocytes. The eye is a highly specialized sensory organ that contains the retina, part of the central nervous system, as well as non-neuronal parts like the transparent vitreous body, ensuring the stability of the eyeball and the clarity of the optical axis. This study utilizes genetically engineered mice, embryonic and adult labeling methods, as well as multicolor immunofluorescence labeling and confocal laser scanning microscopy to comprehensively reveal the characteristics of the hyalocyte population in mice during development and adulthood.

The study confirmed that mouse hyalocytes express various known myeloid cell markers and exhibit a unique immune phenotype compared to retinal microglia. Embryonic pulse labeling revealed that mouse hyalocytes are derived from the yolk sac, with their precursors implanted into the developing eye prenatally. Ultimately, postnatal labeling and xenograft experiments confirmed that hyalocytes are long-lasting and rely on CSF1R (colony stimulating factor 1 receptor) signaling for maintenance, independent of blood-derived monocytes.

This study identifies hyalocytes as long-lived descendants of yolk sac hematopoiesis and emphasizes their role as part of the eye’s innate immune system. As a consequence of longevity, the aging process may lead to hyalocyte dysfunction, thereby contributing to the development of retinal vitreoretinal interface diseases. Therefore, myeloid cell-targeted therapies that modulate the nature of hyalocytes to deliver effects might be an interesting approach to alleviate the burden of retinal vitreoretinal interface diseases.

Keywords include: macrophages, hyalocytes, vitreous body, CX3CR1, labeling mapping, replacement, development, CSF1R. Dennis-Dominik Rosmus and Jana Koch contributed equally to this study.

The research background points out that macrophages play a crucial role in the innate immunity of their hosts. Research over the past decade has shown that tissue-resident macrophages exhibit significant heterogeneity in origin, fate, and function. The generally accepted view today is that myeloid cells originate from different hematopoietic waves during prenatal and postnatal development. The study results reveal that the first batch of tissue-resident macrophages in mice originates from early myeloid progenitor cells (EMPs) that form in the yolk sac during day 8.5 (E8.5) of embryogenesis. These cells further differentiate into groups A1 and CX3CR1-expressing A2, sequentially seeding almost all prenatal tissue-resident macrophage populations. Finally, postnatal labeling and xenograft experiments confirm the longevity of hyalocytes, which depends on CSF1R signaling, and this concludes the Chinese abstract of the paper.

This research not only deepens the understanding of the population of tissue-resident macrophages in the field of ocular immunology but also provides new perspectives and possible intervention strategies for the further development of treatment for ophthalmic diseases.