June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Transcriptional characterization of vitreal hyalocytes in patients with proliferative diabetic retinopathy
Author Affiliations & Notes
  • Stefaniya Boneva
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
  • Julian Wolf
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
    Department of Ophthalmology, Stanford University, Palo Alto, California, United States
  • Malte Jung
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
  • Anja Schlecht
    Institute of Anatomy, Julius-Maximilians-Universitat Wurzburg, Wurzburg, Bayern, Germany
  • Felicitas Bucher
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
  • Gunther R Schlunck
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
  • Hansjuergen Agostini
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
  • Clemens Lange
    Eye Center, Albert-Ludwigs-Universitat Freiburg Medizinische Fakultat, Freiburg, Baden-Württemberg, Germany
    Department of Ophthalmology, St. Franziskus Hospital, Münster, Germany
  • Footnotes
    Commercial Relationships   Stefaniya Boneva None; Julian Wolf None; Malte Jung None; Anja Schlecht None; Felicitas Bucher None; Gunther Schlunck None; Hansjuergen Agostini None; Clemens Lange None
  • Footnotes
    Support  Berta-Ottenstein-Programme for Clinician Scientists, University of Freiburg, Germany; Ernst and Berta Grimmke Foundation, Germany
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2041. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Stefaniya Boneva, Julian Wolf, Malte Jung, Anja Schlecht, Felicitas Bucher, Gunther R Schlunck, Hansjuergen Agostini, Clemens Lange; Transcriptional characterization of vitreal hyalocytes in patients with proliferative diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2041.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Posterior vitreous detachment and vitrectomy mitigate neovascularization growth in proliferative diabetic retinopathy (PDR). Thus, the vitreous body and vitreous macrophages, called hyalocytes, have been suggested as essential participants in the course of PDR in the past. In this study, the transcriptome of diabetic hyalocytes was assessed to gain further insight into their potential contribution to diabetic vitreoretinal disease.

Methods : A total of 52 patients treated by vitrectomy for PDR (n = 20), macular pucker or macular hole (n = 32, controls) were included in this study. Hyalocytes were isolated by flow cytometry, followed by RNA extraction. After RNA sequencing, differentially expressed genes (DEG) and enrichment of genes associated with specific biological processes (Gene Ontology, GO) were analyzed bioinformatically. On the protein level, the expression of 54 proteins was compared between the diabetic and control vitreous by multiplex cytokine analysis. Moreover, factors of interest were stained immunohistochemically in cultured human hyalocytes.

Results : Hyalocytes from PDR patients showed a total of 255 upregulated and 400 downregulated DEG compared to hyalocytes from controls. The transcriptional signature of hyalocytes in PDR was mainly characterized by the enrichment of factors involved in immunological GO processes such as "chemotaxis" (e.g. LGMN, legumain, and EDNRB, endothelin receptor type B) and "leukocyte migration" (e.g., S1PR1, sphingosine-1-phosphatase receptor 1, and MMP9, matrix metallopeptidase 9). In addition, hyalocytes in PDR expressed pro-inflammatory angiogenic factors, e.g. IL6, interleukin 6, which was also significantly increased on the protein level in the diabetic vitreous. Furthermore, enzymes with key functions in hemoglobin catabolism such as HMOX1, heme oxygenase-1, BLVRA, and BLVRB, biliverdin reductases, were among the most prominent factors in diabetic hyalocytes. Finally, cultured diabetic hyalocytes stained positive for CD235, a protein of the human erythrocyte membrane.

Conclusions : Our analysis offers a first characterization of the hyalocyte transcriptome in patients with PDR and strongly suggests that hyalocytes actively contribute to the pro-inflammatory and angiogenic diabetic vitreous milieu. Moreover, hyalocytes appear to be involved in erythrophagocytosis in the diabetic vitreous, which reveals potential therapeutic venues.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×