Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration

Pilotto, Elisabetta; Nacci, Elisabetta Beatrice; Ferrara, Alfonso Massimiliano; Mojà, Gilda De; Zovato, Stefania; Midena, Edoardo

doi:10.3390/jcm9082677

Cited by 6 publications

(8 citation statements)

References 25 publications

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“…Therefore, we analyzed the specific biomarkers of these cell populations in VHL subjects, in particular, focusing on the presence/absence of peripheral RH. Our results showed an overall thinning of pRNFL, mRNFL, and GCL retinal layers in VHL patients compared to controls, probably due to the macular and peripapillary perfusion impairment previously demonstrated [ 15 , 33 ]. We therefore analyzed how pRNFL, mRNFL, and GCL behaved, comparing VHL patients according to the presence or absence of RH.…”

Section: Discussionsupporting

confidence: 67%

“…This increase in number is a consequence of microglia activation, as previously reported in other retinal and systemic diseases. In particular, VEGF overexpression, due to the mutation of pVHL, might contribute to induce the activation of microglia in VHL patients [ 1 , 2 , 3 , 4 , 5 , 6 , 33 , 36 , 37 , 38 , 39 , 40 ]. We therefore hypothesize that pVHL alterations determine a “pre-activation” of the resident microglia.…”

Section: Discussionmentioning

confidence: 99%

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

Pilotto

Midena

Torresin

et al. 2021

Cancers

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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 < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (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.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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

Pilotto

Midena

Torresin

et al. 2021

Cancers

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“…In VHL patients, OCT and OCTA have been mainly used to study posterior pole RH or macular capillary changes related to RH [29][30][31][32] . To the best of our knowledge, this is the first OCT and OCTA study investigating the structural and perfusion characteristics of the peripapillary nerve fiber layer, in which glial cells, neurons and capillaries of the radial peripapillary capillary plexus interact.…”

Section: Discussionmentioning

confidence: 99%

“…The inbuilt software automatically generated the enface OCTA image of the radial peripapillary capillary plexus, which is the radial capillary monolayer network encircling the optic disc 11 , 13 . As previously described 29 in order to guarantee high quality OCTA images, only images with a signal strength more than 30 in “Q score” (on a scale of 0 to 40 for Spectralis, Heidelbeerg), were analysed 36 , 37 . Correct foveal centration of the scans was obtained with the inbuilt eye tracking system.…”

Section: Methodsmentioning

confidence: 99%

Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel–Lindau disease: an OCT and OCT angiography study

Pilotto

Nacci

Mojà

et al. 2021

Sci Rep

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Von Hippel–Lindau (VHL) disease is an autosomal dominant genetic disease caused by VHL gene mutation. Retinal hemangioblastomas (RH) are vascularized tumors and represent the main ocular manifestation of the disease. Histopathologically, RH are composed of capillary vessels and stromal cells, the neoplastic population of the lesion. The origin of these stromal cells remains controversial, even if they are hypothesized to be glial cells. The aim of the present study was to investigate neuronal and microvascular changes of the peripapillary retinal nerve fiber layer, in which glial cells, neurons and capillaries (the radial peripapillary capillary plexus) interact. VHL patients with or without peripheral RH were enrolled and compared to healthy controls. Mean peripapillary retinal nerve fiber layer (pRNFL) thickness was measured by means of optical coherence tomography (OCT). The following vascular parameters of the radial peripapillary capillary plexus were quantified using OCT angiography: Vessel Area Density,Vessel Length Fraction, Vessel Diameter Index and Fractal Dimension. One hundred and nine eyes of 61 patients, and 56 eyes of 28 controls were consecutively studied. Mean pRNFL was significantly thinner in VHL eyes without RH versus eyes with RH and controls. Mean pRNFL thickness did not differ between VHL eyes with RH and controls. All OCTA vascular parameters were reduced in VHL eyes with or without RH versus controls, with significative difference for Vessel Diameter Index. The same OCTA parameters did not significantly differ between VHL eyes with or without RH. In VHL eyes without RH, pRNFL thinning may be the consequence of impaired perfusion of the radial peripapillary capillary plexus, while the increase of pRNFL thickness in VHL eyes with RH may depend on possible activation and proliferation of the other RNFL resident cells, the glial cells.

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“…In contrast to the study by Lu et al, patients with VHL disease in this study had lower numbers of retinal vessels in the macular area, and the vessels were thinner in diameter compared to healthy controls. These changes were more pronounced in the superficial capillary plexus [ 147 ]. Another study by Pilotto et al showed thinning of the peripapillary retinal nerve fiber layer in VHL patients without a retinal hemangioblastoma [ 148 ].…”

Section: Clinical and Genetic Features Of Selected Manifestations Of ...mentioning

confidence: 99%

The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis

Hudler

Urbančič

2022

Genes

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Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic syndrome stemming from germline disease-associated variants of the VHL tumor suppressor gene on chromosome 3. VHL is involved, through the EPO-VHL-HIF signaling axis, in oxygen sensing and adaptive response to hypoxia, as well as in numerous HIF-independent pathways. The diverse roles of VHL confirm its implication in several crucial cellular processes. VHL variations have been associated with the development of VHL disease and erythrocytosis. The association between genotypes and phenotypes still remains ambiguous for the majority of mutations. It appears that there is a distinction between erythrocytosis-causing VHL variations and VHL variations causing VHL disease with tumor development. Understanding the pathogenic effects of VHL variants might better predict the prognosis and optimize management of the patient.

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Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration

Cited by 6 publications

References 25 publications

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

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

Structural and microvascular changes of the peripapillary retinal nerve fiber layer in Von Hippel–Lindau disease: an OCT and OCT angiography study

The Role of VHL in the Development of von Hippel-Lindau Disease and Erythrocytosis

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