NGF in Inflammatory and Neurodegenerative Diseases of the Eye: New Findings Supporting Neuroprotection and Proper Tissue Remodeling in Vitreoretinal Disorders

Esposito, Graziana; Balzamino, Bijorn Omar; Bruno, Luca; Cacciamani, Andrea; Micera, Alessandra

doi:10.1007/978-3-030-74046-7_18

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…In previous studies, IL1β and IFNγ were associated with iNOS gene activation while p65NFκB and STAT1 were reported for iNOS gene transcription [26]. The influence of VEGF-A, IL6, and IL8 (angiogenic factors) and MIP1α (leucocyte recruiter molecule) in vitreoretinal disorders has been previously reported for proliferative and/or diabetic retinopathies [17,56]. Although, VEGF and Ang-2 synergistically influence the local angiogenesis in retinal diseases, we did not observe significant changes between vitreal fluids depending on ERM severity [54][55][56][57].…”

Section: Discussionmentioning

confidence: 82%

“…The influence of VEGF-A, IL6, and IL8 (angiogenic factors) and MIP1α (leucocyte recruiter molecule) in vitreoretinal disorders has been previously reported for proliferative and/or diabetic retinopathies [17,56]. Although, VEGF and Ang-2 synergistically influence the local angiogenesis in retinal diseases, we did not observe significant changes between vitreal fluids depending on ERM severity [54][55][56][57]. No significant changes were also found for IFNγ, IL18, and IL22 (proinflammatory cytokines) depending on disease severity.…”

Section: Discussionmentioning

confidence: 87%

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Short-Term In Vitro ROS Detection and Oxidative Stress Regulators in Epiretinal Membranes and Vitreous from Idiopathic Vitreoretinal Diseases

Balzamino

Dinice

Cacciamani

et al. 2022

BioMed Research International

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Background. A plethora of inflammatory, angiogenic, and tissue remodeling factors has been reported in idiopathic epiretinal membranes (ERMs). Herein we focused on the expression of a few mediators (oxidative, inflammatory, and angiogenic/vascular factors) by means of short-term vitreal cell cultures and biomolecular analysis. Methods. Thirty-nine (39) ERMs and vitreal samples were collected at the time of vitreoretinal surgery and biomolecular analyses were performed in clear vitreous, vitreal cell pellets, and ERMs. ROS products and iNOS were investigated in adherent vitreal cells and/or ERMs, and iNOS, VEGF, Ang-2, IFNγ, IL18, and IL22 were quantified in vitreous (ELISA/Ella, IF/WB); transcripts specific for iNOS, p65NFkB, KEAP1, NRF2, and NOX1/NOX4 were detected in ERMs (PCR). Biomolecular changes were analyzed and correlated with disease severity. Results. The higher ROS production was observed in vitreal cells at stage 4, and iNOS was found in ERMs and increased in the vitreous as early as at stage 3. Both iNOS and NOX4 were upregulated at all stages, while p65NFkB was increased at stage 3. iNOS and NOX1 were positively and inversely related with p65NFkB. While NOX4 transcripts were always upregulated, NRF2 was upregulated at stage 3 and inverted at stage 4. No significant changes occurred in the release of angiogenic (VEGF, Ang-2) and proinflammatory (IL18, IL22 and IFNγ) mediators between all stages investigated. Conclusions. ROS production was strictly associated with iNOS and NOX4 overexpression and increased depending on ERM stadiation. The higher iNOS expression occurred as early as stage 3, with respect to p65NFkB and NRF2. These last mediators might have potential prognostic values in ERMs as representative of an underneath retinal damage.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 87%

Short-Term In Vitro ROS Detection and Oxidative Stress Regulators in Epiretinal Membranes and Vitreous from Idiopathic Vitreoretinal Diseases

Balzamino

Dinice

Cacciamani

et al. 2022

BioMed Research International

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“…Multiple linked events have been observed in cultured UV-exposed FBs, including the release of chemokines, cytokines, growth/angiogenic factors, and several profibrogenic mediators [ 2 , 34 ]. Since UV-exposed FBs might affect the conjunctival microenvironment and epithelia-stromal crosstalk and NGF can exert pleiotropic effects at the ocular surface [ 11 , 27 , 35 ], a possible NGF effect in counteracting UV-protein signature was prospected and investigated. A single UV insult with no apoptotic or necrotic response (sub-cytotoxic effects) was tested.…”

Section: Discussionmentioning

confidence: 99%

“…Highly involved in the homeostasis of the visual system, the nerve growth factor (NGF), the tyrosine kinase trkA NGF , and the pan-neurotrophin p75 NGF receptors have been recently reported to have multiple effects in UV-exposed tissues and cells [ 24 , 25 , 26 , 27 , 28 ]. Since NGF has been proven as (i), protective and therapeutic for damaged corneal and conjunctival epithelial cells; (ii), profibrogenic for corneal and conjunctival fibroblasts/myofibroblasts; and (iii), neuroprotective for retinal cells [ 10 , 11 ], the aim of this study was to explore the effect of NGF supplementation in UV-exposed conjunctival FBs by analyzing a few selected targets (inflammatory and epigenetic factors) previously linked to UV-exposed cells.…”

Section: Introductionmentioning

confidence: 99%

Nerve Growth Factor (NGF) as Partaker in the Modulation of UV-Response in Cultured Human Conjunctival Fibroblasts

Esposito

Balzamino

Rocco

et al. 2022

IJMS

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Corroborating data sustain the pleiotropic effect of nerve growth factor (NGF) in the protection of the visual system from dangerous stimuli, including ultraviolet (UV). Since UV exposure might promote ocular surface changes (conjunctival inflammation and matrix rearrangement), as previously reported from in vivo studies sustaining some protective NGF effects, in vitro cultures of human conjunctival fibroblasts (FBs) were developed and exposed to a single UV exposure over 15 min (0.277 W/m2), either alone or supplemented with NGF (1–10–100 ng/mL). Conditioned media and cell monolayers were collected and analyzed for protein release (ELISA, ELLA microfluidic) and transcript expression (real-time PCR). A specific “inflammatory to remodeling” pattern (IL8, VEGF, IL33, OPN, and CYR61) as well as a few epigenetic transcripts (known as modulator of cell differentiation and matrix-remodeling (DNMT3a, HDAC1, NRF2 and KEAP1)) were investigated in parallel. UV-exposed FBs (i), showed no proliferation or significant cytoskeleton rearrangement; (ii), displayed a trkANGFR/p75NTR phenotype; and (iii), synthesized/released IL8, VEGF-A, IL33, OPN, and CYR61, as compared to unexposed ones. NGF addition counteracted IL8, IL33, OPN, and CYR61 protein release merely at lower NGF concentrations but not VEGF. NGF supplementation did not affect DNMT3a or HDAC1 transcripts, while it significantly upregulated NRF2 at lowest NGF doses and did not change KEAP1 expression. Taken together, a single UV exposure activated conjunctival FBs to release pro-inflammatory/fibrogenic factors in association with epigenetic changes. The effects were selectively counteracted by NGF supplementation in a dose-dependent fashion, most probably accountable to the trkANGFR/p75NTR phenotype. Further in vitro studies are underway to better understand this additional NGF pleiotropic effect. Since UV-shield impairments represent a worldwide alert and UV radiation can slowly affect ocular surface homeostasis (photo-ageing, cataract) or might exacerbate ocular diseases with a preexisting fibrosis (pterygium, VKC), these findings on NGF modulation of UV-exposed FBs might provide additional information for protecting the ocular surface (homeostasis) from low-grade long-lasting UV insults.

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“…Furthermore, an imbalanced ratio between proNGF and mature NGF seems to be an early indicator for complications from diabetes generally 18 . Improper regulation or disfunction of NGF may also be implicated in neurodegenerative disorders such as Alzheimer's disease [19][20][21][22] , age related macular degeneration [23][24][25][26] , retinal injury 27 , and multiple sclerosis 28 , and NGF has also been investigated for a therapeutic role in the neurodegenerative disease glaucoma 24 . Since its discovery and isolation 29,30 , it is recognized that NGF has effects on the development of nervous systems [31][32][33] and plays a key role in adult nociceptive modulation 34,35 .…”

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confidence: 99%

Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry

Walsh

Palandra

Goihberg

et al. 2023

Sci Rep

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Abstractβ-Nerve growth factor (NGF) is a neurotrophin that plays a critical role in fetal development during gestation. ProNGF is the precursor form of NGF with a distinct biological profile. In order to investigate the role of NGF and proNGF in pregnant human females, a sensitive and selective immunoaffinity liquid chromatography-tandem mass spectrometry assay was developed and qualified to simultaneously measure the levels of total NGF (tNGF; sum of mature and proNGF) and proNGF using full and relative quantification strategies, respectively. The assay was used to determine serum tNGF and proNGF levels in the three gestational trimesters of pregnancy and in non-pregnant female controls. Mean tNGF ± SD were 44.6 ± 12.3, 42.6 ± 9.3, 65.4 ± 17.6 and 77.0 ± 17.8 pg/mL for non-pregnant, first, second, and third trimesters, respectively, demonstrating no significant increase in circulating tNGF between the control and the first trimester, and a moderate yet significant 1.7-fold increase through gestation. proNGF levels during the first trimester were unchanged compared to control. In contrast to tNGF, however, proNGF levels during gestation remained stable without significant changes. The development of this sensitive, novel immunoaffinity duplexed assay for both tNGF and proNGF is expected to enable further elucidation of the roles these neurotrophins play in human pregnancy as well as other models.

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NGF in Inflammatory and Neurodegenerative Diseases of the Eye: New Findings Supporting Neuroprotection and Proper Tissue Remodeling in Vitreoretinal Disorders

Cited by 9 publications

References 25 publications

Short-Term In Vitro ROS Detection and Oxidative Stress Regulators in Epiretinal Membranes and Vitreous from Idiopathic Vitreoretinal Diseases

Short-Term In Vitro ROS Detection and Oxidative Stress Regulators in Epiretinal Membranes and Vitreous from Idiopathic Vitreoretinal Diseases

Nerve Growth Factor (NGF) as Partaker in the Modulation of UV-Response in Cultured Human Conjunctival Fibroblasts

Analysis of β-nerve growth factor and its precursor during human pregnancy by immunoaffinity-liquid chromatography tandem mass spectrometry

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