Boneva Lab – Immunology of the Vitreoretinal Interface
Research Focus
Hyalocytes represent a population of macrophages residing at the vitreoretinal interface. Comprehensive understanding of their functions and immunological significance has only recently emerged unraveling critical roles of hyalocytes in the developing, healthy, aging, and diseased eye including their contribution to severe conditions of the posterior eye segment.
Ongoing research in the Boneva Lab focuses on the impact of hyalocytes in the course of proliferative vitreoretinopathy, a devastating complication of long-standing retinal detachment. We have developed a porcine vitreous cell culture model to mimic the formation of epiretinal stellate folds as hallmark of the disease. Further projects will concentrate on the translation of knowledge acquired in vitro to the human situation and on developing potential pharmacotherapeutic options to target and modify hyalocyte functions. Moreover, we seek to characterize comprehensively neovascularization tissue extracted from the eyes of patients with advanced macular degeneration or proliferative diabetic retinopathy. We hypothesize that the common denominator of all these severe conditions of the vitreoretinal interface are resident immune cells of the posterior eye segment, among them, most possibly also hyalocytes. By applying state-of-the art techniques, such as flow cytometry-based sorting, high-throughput transcriptional analyses by RNA sequencing and single-cell proteomic analyses coupled with sophisticated imaging techniques we aim to decipher the alleged dual role of hyalocytes balancing benign and malign properties and a potential deleterious switch from promoters of homeostasis to pernicious effects in disease.
Dr. Stefaniya Boneva, MD, FEBO
stefaniya.boneva@uniklinik-freiburg.de
Group Members
- Gabriele Prinz, technician
- Dr. Quang Vinh Ngo, MD
- Anastasia Sushich, MD student
- Nina Martius, MD student
- Jacqueline Jauch, MD student (funded by TANDEM PRO, a scholarship of the Medical Faculty, University of Freiburg)
- Suzanne Guth, MD student
Collaborations
- Prof. Dr. Dr. Clemens Lange, MD, PhD, Department of Ophthalmology at St. Franziskus Hospital, Münster
- Prof. J. Sebag, MD, FACS, FRCOphth, FARVO, Doheny Eye Institute at UCLA, Los Angeles, CA, USA
- Prof. Dr. Peter Wieghofer, PhD, Cellular Neuroanatomy, Institute of Theoretical Medicine at Augsburg University
- Prof. Dr. Dr. Bertram Bengsch, MD, PhD, Department of Medicine II at University of Freiburg
- Toco Y. P. Chui, PhD, and Prof. Richard B. Rosen, MD, Department of Ophthalmology at New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA
Funding
- Deutsche Forschungsgemeinschaft (DFG)
- Berta-Ottenstein-Programme for (Advanced) Clinician Scientists, Medical Faculty, University of Freiburg
- Grimmke Foundation
- Jackstädt Foundation
- German Retina Society (Dr. Werner Jackstädt Prize)
- German Society of Ophthalmology
- Freunde der Universitäts-Augenklinik Freiburg e.V.
Publications
ORCID ID: 0000-0002-9811-2160
Selected publications
Boneva SK, Wolf J, Rosmus DD, Schlecht A, Prinz G, Laich Y, Boeck M, Zhang P, Hilgendorf I, Stahl A, Reinhard T, Bainbridge J, Schlunck G, Agostini H, Wieghofer P, Lange CAK. Transcriptional profiling uncovers human hyalocytes as a unique innate immune cell population. Front Immunol. 2020;11:567274. doi:10.3389/fimmu.2020.567274
Wieghofer P, Hagemeyer N, Sankowski R, Schlecht A, Staszewski O, Amann L, Gruber M, Koch J, Hausmann A, Zhang P, Boneva S, Masuda T, Hilgendorf I, Goldmann T, Böttcher C, Priller J, Rossi FM, Lange C, Prinz M. Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling. EMBO J. 2021;40(6):e105123. doi:10.15252/embj.2020105123
Boneva SK, Wolf J, Hajdú RI, Prinz G, Salié H, Schlecht A, Killmer S, Laich Y, Faatz H, Lommatzsch A, Busch M, Bucher F, Stahl A, Böhringer D, Bengsch B, Schlunck G, Agostini H, Lange CAK. In-depth molecular characterization of neovascular membranes suggests a role for hyalocyte-to-myofibroblast transdifferentiation in proliferative diabetic retinopathy. Front Immunol. 2021;12:757607. doi:10.3389/fimmu.2021.757607
Wolf J, Boneva S, Rosmus DD, Agostini H, Schlunck G, Wieghofer P, Schlecht A, Lange C. Deciphering the molecular signature of human hyalocytes in relation to other innate immune cell populations. Invest Ophthalmol Vis Sci. 2022;63(3):9. doi:10.1167/iovs.63.3.9
Boneva S, Wolf J, Wieghofer P, Sebag J, Lange C. Hyalocyte functions and immunology. Expert Review of Ophthalmology. 2022;17(4):249-262. doi:10.1080/17469899.2022.2100763
Laich Y, Wolf J, Hajdu RI, Schlecht A, Bucher F, Pauleikhoff L, Busch M, Martin G, Faatz H, Killmer S, Bengsch B, Stahl A, Lommatzsch A, Schlunck G, Agostini H, Boneva S*, Lange C*. Single-cell protein and transcriptional characterization of epiretinal membranes from patients with proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 2022;63(5):17. doi:10.1167/iovs.63.5.17
*contributed equally
Boneva S, Wolf J, Jung M, Prinz G, Chui T, Jauch J, Drougard A, Pospisilik, Schlecht A, Bucher F, Rosen R, Agostini H, Schlunck G, Lange C. The multifaceted role of vitreous hyalocytes: Orchestrating inflammation, angiomodulation and erythrophagocytosis in proliferative diabetic retinopathy. Journal of Neuroinflammation. 2024;21(1):297. doi.org/10.1186/s12974-024-03291-5
