Deciphering the Molecular Signature of Human Hyalocytes in Relation to Other Innate Immune Cell Populations

Abstract

Purpose Hyalocytes are the tissue-resident innate immune cell population of the vitreous body with important functions in health and vitreoretinal disease. The purpose of this study is to gain new insights into the biology and function of human hyalocytes in comparison to other innate immune cells. Methods The present study applies fluorescence-activated cell sorting and RNA sequencing to compare the transcriptional profiles of human hyalocytes, retinal microglia (rMG) and classical, intermediate, and non-classical monocytes isolated from the same patients. Immunohistochemistry was applied for morphological characterization of human hyalocytes. Results Pairwise analysis indicates distinct differences between hyalocytes and monocytes, whereas a high degree of similarity to rMG is apparent, with comparable expression levels of established microglia markers, such as TREM2 , P2RY12 , and TMEM119 . Among the top expressed genes in hyalocytes, SPP1 , CD74 , and C3 , were significantly upregulated when compared with monocytes. Despite the high level of similarity of hyalocytes and rMG, ten highly expressed genes in hyalocytes compared to microglia were identified, among them FOS , DUSP1 , and EGR2 . Conclusions This study reveals a high degree of similarity between hyalocytes and retinal microglia. Nevertheless, hyalocytes exhibit some expression differences that may adapt them to the specific needs of the vitreous and provide the basis for deciphering the multiple roles of this fascinating cell population in health and vitreoretinal diseases.

Changes in macrophage-like cells characterized by en face optical coherence tomography after retinal stroke

“…There are two kinds of specific resident macrophages on the normal inner limiting membrane: hyalocyte and microglia ( 15 ). A previous study revealed distinct differences between hyalocytes and monocytes, but a high degree of similarity was observed between these two cells ( 26 ). Although we could not differentiate microglia and hyalocytes based on label-free en face OCT, cumulative evidence has shown that both cells undergo proliferation and activation in neuroinflammation ( 12 , 27 , 28 ).…”

Macrophages in close proximity to the vitreoretinal interface are potential biomarkers of inflammation during retinal vascular disease

“…Transcriptional profiling of human hyalocytes finds that these cells present antigens and participate in immune privilege of the vitreous [ 35 ]. Compared to retinal microglia, human hyalocytes were enriched for angiogenesis and chemotaxis gene ontology terms, suggesting a potential role for hyalocytes in the inflammatory component of DR and RVO [ 36 ]. In addition, both diseases can cause vision loss from tractional retinal detachments that form as neovascular membranes contract at the vitreoretinal interface.…”

Macrophage-like Cells Are Increased in Patients with Vision-Threatening Diabetic Retinopathy and Correlate with Macular Edema

“…Vitreal hyalocytes are another potential MLC identity. Hyalocytes are resident macrophages of the vitreous that present antigens, participate in immune privilege, and express pro-angiogenic and pro-chemotactic transcriptional profiles [ 22 , 23 ]. Thus, MLCs could include vitreal hyalocytes promoting angiogenesis and immune cell infiltration in DME eyes.…”