The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy
Abstract Background Despite great advances in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. While resident vitreous macrophages called hyalocytes have been implicated in the pathophysiology of vitreoretinal proliferativ...
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BMC
2024-11-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-024-03291-5 |
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| author | Stefaniya K. Boneva Julian Wolf Malte Jung Gabriele Prinz Toco Y. P. Chui Jacqueline Jauch Anne Drougard J. Andrew Pospisilik Anja Schlecht Felicitas Bucher Richard B. Rosen Hansjürgen Agostini Günther Schlunck Clemens A. K. Lange |
| author_facet | Stefaniya K. Boneva Julian Wolf Malte Jung Gabriele Prinz Toco Y. P. Chui Jacqueline Jauch Anne Drougard J. Andrew Pospisilik Anja Schlecht Felicitas Bucher Richard B. Rosen Hansjürgen Agostini Günther Schlunck Clemens A. K. Lange |
| author_sort | Stefaniya K. Boneva |
| collection | DOAJ |
| description | Abstract Background Despite great advances in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. While resident vitreous macrophages called hyalocytes have been implicated in the pathophysiology of vitreoretinal proliferative disease previously, little is known about their exact role in PDR. In this study, we address molecular and cellular alterations in the vitreous of PDR patients as a means towards assessing the potential contribution of hyalocytes to disease pathogenesis. Results A total of 55 patients were included in this study encompassing RNA-Sequencing analysis of hyalocytes isolated from the vitreous of PDR and control patients, multiplex immunoassay and ELISA analyses of vitreous samples from PDR and control patients, as well as isolation and immunohistochemical staining of cultured porcine hyalocytes. Transcriptional analysis revealed an enhanced inflammatory response of hyalocytes contributing to the cytokine pool within the vitreous of PDR patients by expressing interleukin-6, among others. Further, increased angiopoietin-2 expression indicated that hyalocytes from PDR patients undergo a proangiogenic shift and may thus mediate the formation of retinal neovascularizations, the hallmark of PDR. Finally, RNA-Sequencing revealed an upregulation of factors known from hemoglobin catabolism in hyalocytes from PDR patients. By immunohistochemistry, cultured porcine hyalocytes exposed to red blood cells were shown to engulf and phagocytose these, which reveals hyalocytes’ potential to dispose of erythrocytes. Thus, our data suggest a potential role for vitreous macrophages in erythrophagocytosis and, thereby, clearance of vitreous hemorrhage, a severe complication of PDR. Conclusion Our results strongly indicate a critical role for vitreous hyalocytes in key pathophysiological processes of proliferative diabetic retinopathy: inflammation, angiomodulation and erythrophagocytosis. Immunomodulation of hyalocytes may thus prove an essential novel therapeutic approach in diabetic vitreoretinal disease. |
| format | Article |
| id | doaj-art-827468ebd85945bda91aa82c724d8c7e |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Journal of Neuroinflammation |
| spelling | doaj-art-827468ebd85945bda91aa82c724d8c7e2024-12-01T12:37:52ZengBMCJournal of Neuroinflammation1742-20942024-11-0121111610.1186/s12974-024-03291-5The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathyStefaniya K. Boneva0Julian Wolf1Malte Jung2Gabriele Prinz3Toco Y. P. Chui4Jacqueline Jauch5Anne Drougard6J. Andrew Pospisilik7Anja Schlecht8Felicitas Bucher9Richard B. Rosen10Hansjürgen Agostini11Günther Schlunck12Clemens A. K. Lange13Eye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgDepartment of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, Icahn School of Medicine at Mount SinaiEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgDepartment of Epigenetics, Van Andel Research InstituteDepartment of Epigenetics, Van Andel Research InstituteEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgDepartment of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, Icahn School of Medicine at Mount SinaiEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgEye Center, Medical Center, Faculty of Medicine, University Medical Center FreiburgAbstract Background Despite great advances in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. While resident vitreous macrophages called hyalocytes have been implicated in the pathophysiology of vitreoretinal proliferative disease previously, little is known about their exact role in PDR. In this study, we address molecular and cellular alterations in the vitreous of PDR patients as a means towards assessing the potential contribution of hyalocytes to disease pathogenesis. Results A total of 55 patients were included in this study encompassing RNA-Sequencing analysis of hyalocytes isolated from the vitreous of PDR and control patients, multiplex immunoassay and ELISA analyses of vitreous samples from PDR and control patients, as well as isolation and immunohistochemical staining of cultured porcine hyalocytes. Transcriptional analysis revealed an enhanced inflammatory response of hyalocytes contributing to the cytokine pool within the vitreous of PDR patients by expressing interleukin-6, among others. Further, increased angiopoietin-2 expression indicated that hyalocytes from PDR patients undergo a proangiogenic shift and may thus mediate the formation of retinal neovascularizations, the hallmark of PDR. Finally, RNA-Sequencing revealed an upregulation of factors known from hemoglobin catabolism in hyalocytes from PDR patients. By immunohistochemistry, cultured porcine hyalocytes exposed to red blood cells were shown to engulf and phagocytose these, which reveals hyalocytes’ potential to dispose of erythrocytes. Thus, our data suggest a potential role for vitreous macrophages in erythrophagocytosis and, thereby, clearance of vitreous hemorrhage, a severe complication of PDR. Conclusion Our results strongly indicate a critical role for vitreous hyalocytes in key pathophysiological processes of proliferative diabetic retinopathy: inflammation, angiomodulation and erythrophagocytosis. Immunomodulation of hyalocytes may thus prove an essential novel therapeutic approach in diabetic vitreoretinal disease.https://doi.org/10.1186/s12974-024-03291-5HyalocytesVitreous macrophagesProliferative diabetic retinopathyInflammationAngiomodulationErythrophagocytosis |
| spellingShingle | Stefaniya K. Boneva Julian Wolf Malte Jung Gabriele Prinz Toco Y. P. Chui Jacqueline Jauch Anne Drougard J. Andrew Pospisilik Anja Schlecht Felicitas Bucher Richard B. Rosen Hansjürgen Agostini Günther Schlunck Clemens A. K. Lange The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy Journal of Neuroinflammation Hyalocytes Vitreous macrophages Proliferative diabetic retinopathy Inflammation Angiomodulation Erythrophagocytosis |
| title | The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy |
| title_full | The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy |
| title_fullStr | The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy |
| title_full_unstemmed | The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy |
| title_short | The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy |
| title_sort | multifaceted role of vitreous hyalocytes orchestrating inflammation angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy |
| topic | Hyalocytes Vitreous macrophages Proliferative diabetic retinopathy Inflammation Angiomodulation Erythrophagocytosis |
| url | https://doi.org/10.1186/s12974-024-03291-5 |
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