Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid

Puthenparampil, Marco; Torresin, Tommaso; Franciotta, Silvia; Marin, Annachiara; Napoli, Federica De; Mauceri, Valentina Annamaria; Miante, Silvia; Pilotto, Elisabetta; Midena, Edoardo; Gallo, Paolo

doi:10.3389/fimmu.2022.852183

Cited by 16 publications

(9 citation statements)

References 37 publications

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“…Activated microglia are one of the essential neurotoxic mediators of neuroinflammation ( Deng et al, 2009 ; Zhao et al, 2015 ). They rapidly move to damage sites and secrete pro-inflammatory factors (e.g., IL-1β , IL-6 , TNF-α ), chemokines (e.g., CCL2 , CCL4 , CXCL10 ) resulting in secondary damage to neuronal death, thereby accelerating the disease progression of patients ( Wu et al, 2021 ; Puthenparampil et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Feng

Qin

et al. 2023

Front. Mol. Neurosci.

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Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during retinal development. In certain retinal diseases, the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea). Furthermore, continuously activated microglia secrete inflammatory factors and expedite the loss of the blood-retinal barrier which causes irreversible damage to the secondary death of neurons. In this review, we support microglia can be a potential cellular therapeutic target in retinopathy. We briefly describe the relevance of microglia to the retinal vasculature and blood-retinal barrier. Then we discuss the signaling pathway related to how microglia move to their destinations and regulate vascular regeneration. We summarize the properties of microglia in different retinal disease models and propose that reducing the number of pro-inflammatory microglial death and conversing microglial phenotypes from pro-inflammatory to anti-inflammatory are feasible for treating retinal neovascularization and the damaged blood-retinal barrier (BRB). Finally, we suppose that the unique properties of microglia may aid in the vascularization of retinal organoids.

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Section: Introductionmentioning

confidence: 99%

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Feng

Qin

et al. 2023

Front. Mol. Neurosci.

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“…The origin of HRF remains controversial and activated microglia or lipoprotein exudation are among the suspected causes [ 18 ], [ 19 ]. Growing evidence suggests that idiopathic epiretinal macular membranes present with lacunar structures with inflammatory or necrotic characteristics [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial

Luan,

Wang,

Gong

et al. 2024

BMC Ophthalmol

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Background We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. Methods A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. Results BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). Conclusions We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. Trial registration The trail has been registered at Chinese Clinical Trail Registry(https://www.chictr.org.cn) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

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“…The main and widely accepted hypotheses refer HRF as aggregates of activated resident retinal microglial cells, playing a pivotal role in retinal inflammation [7][8][9][10][11][12]. An increased number of HRF was recently found after intraocular surgical procedure, and in patients suffering from Multiple Sclerosis, a typical neuroinflammatory disease, confirming HRF inflammatory nature [13][14][15].…”

Section: Introductionmentioning

confidence: 95%

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

et al. 2022

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Purpose 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. Methods In this cross-sectional study, patients with VHL underwent complete ophthalmological examination and OCT with HRA + OCT Spectralis. HRF were manually identified and calculated in inner (IR), outer (OR) and full retina. Age-matched healthy subjects were enrolled as controls. Results 113 eyes of 63 VHL patients and 56 eyes of 28 healthy subjects were evaluated. HRF number was significantly higher in VHL than in controls in IR (28.06 ± 7.50 vs 25.25 ± 6.64, p = 0.042). No difference was observed in OR and in full retina (OR: 7.73 ± 2.59 vs 7.95 ± 2.51, p = 0.599; full retina: 35.79 ± 8.77 vs 33.20 ± 7.47, p = 0.093). Conclusion The increase of HRF, which mirror retinal microglial activation, characterizes VHL eyes. The role of activated microglia in the retina of VHL eyes needs to be better investigated, mainly considering local VHL disease manifestations.

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Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid

Cited by 16 publications

References 37 publications

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial

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

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