Retinal Glial Cells in Von Hippel–Lindau Disease: A Novel Approach in the Pathophysiology of Retinal Hemangioblastoma

Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p p p p p p p p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease

Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease

von Hippel-Lindau (VHL) disease is caused by a mutation of the VHL gene and characterized by the development of retinal hemangioblastomas (RH). Current pathophysiologic mechanisms of RH development and progression are still insufficient to predict RH behavior. VHL gene is involved in the cellular response to hypoxia and in many intracellular signaling pathways expressed both in angiogenesis and inflammation. Optical coherence tomography (OCT) allows to identify hyper-reflective retinal foci (HRF) known as aggregates of activated microglial cells as possible in vivo biomarker of local inflammation. The aim of the present study was to investigate the presence of HRF in patients with genetically confirmed VHL disease