Researchers uncover origin of phagocytes in the vitreous body of the eye

(Image Credit: AdobeStock/Vladimir Voronin)

A team of researchers at the Faculty of Medicine at the University of Augsburg in Germany have gained new insight into macrophages, immune cells in the eye.

According to a news release, macrophages, also known as scavenger cells, are part of the immune system, destroying invading pathogens, and are found in the organs and the bloodstream.¹

Prof. Peter Wieghofer, professor of cellular neuroanatomy, and a researcher at the Faculty of Medicine at the University of Augsburg in Germany, has led the research, with the results published in the Journal of Neuroinflammation.²

The researchers showed in their work that in the eye of the mouse, macrophages are already forming in the vitreous body in the embryonic stage. For a number of years, researchers believed that hyalocytes regularly regenerate from blood cells.

Fundamental research as a foundation

“The macrophages in the vitreous body develop before birth, settle in the vitreous body and stay there throughout the course of life, just like the macrophages in the retina adjacent to the vitreous body, the so-called microglia,” Wieghofer explained, pointing out that since they are not, as previously thought, renewed from cells in the blood, immunological aging processes can lead to cellular dysfunction and thus contribute to the development of diseases of the vitreous body and the retina.

Wieghofer added that the team has contributed to fundamental research, which concerns scientific questions that are initially concerned with gaining a better understanding of complex functions of the body in order to gain new fundamental insights. While it isn’t immediately known how this knowledge can be used, all forms of therapy, the development of medications, and an understanding of how diseases develop are always based on the findings of fundamental research.²

“In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood,” the researchers wrote. “We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia.”

Moreover, embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes.²

Hope for diabetic retinopathy

The researchers, in their work, may have uncovered a starting point for the therapy of all diseases that affect the hyalocytes of the vitreous body as well as the neighboring retina, as for example with diabetic retinopathy.

“The inflammatory component of diabetic retinopathy is essentially transmitted by macrophages, which are beneficial in the early stages but harmful where there is chronic inflammation, where they can even promote vascularization, namely the formation of new blood cells,” Wieghofer pointed out in the news release. “We hope that this harmful inflammatory reaction may someday be addressed through therapeutic approaches that act on the hyalocytes and reduce their influence on the pathological formation of new blood cells. This would reduce the danger of spontaneous hemorrhaging and reduce the risk of patient blindness.”

Researchers have found another area in which hyalocytes play a key role is in defects concerning the breakdown of vessels in the vitreous body during prenatal development. The team noted that these defects ultimately can lead to severe hemorrhages and blindness within a very short period of time following birth. When it comes to diabetic retinopathy, macrophages can play a role in the development of harmful blood vessels, making them a part of the breaking down of superfluous vessels.^1,2

Moreover, the researchers noted in the study it identifies hyalocytes as the long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye.²

“As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases,” they wrote.

As a result, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface.

“The new findings also offer an interesting approach for potential therapies here,” Wieghofer concluded. “The better we understand the fundamental properties of these cells, the more likely we can influence diseases at the interface of the retina and vitreous body, reducing the severity of such diseases, thus having a lasting impact on the lives of patients.”

References:

1. Origin of phagocytes in the vitreous body of the eye discovered. EurekAlert! Published August 19, 2024. Accessed August 20, 2024. https://www.eurekalert.org/news-releases/1054972

2. Rosmus, DD., Koch, J., Hausmann, A. et al. Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body. J Neuroinflammation 21, 168 (2024). https://doi.org/10.1186/s12974-024-03110-x