New Biomarker Combination Related to Oxidative Stress and Inflammation in Primary Open-Angle Glaucoma

Dammak, Azza; Naves, Juan E.; Huete-Toral, Fernando; Carracedo, Gonzalo

doi:10.3390/life13071455

Cited by 6 publications

(2 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously reported the axonal-protective effects of ripasudil in a tumor necrosis factor (TNF)-induced axonal damage model [ 7 ] and demonstrated the axonal-protective effects of brimonidine in the TNF-induced axonal damage model [ 8 ]. There have been several recent reports showing a close relationship between TNF and glaucoma [ 9 , 10 ]. Those associations are supported by previous studies showing that increased expression of TNF and TNF receptors were observed in RGCs and the optic nerve head of patients with glaucoma [ 11 ] and that TNF-mediated cell death is involved in the neurodegeneration process of glaucoma [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Axonal protection by combination of ripasudil and brimonidine with upregulation of p-AMPK in TNF-induced optic nerve degeneration

Otsubo,

Sase,

Tsukahara

et al. 2024

Int Ophthalmol

View full text Add to dashboard Cite

Purpose The ROCK inhibitor ripasudil hydrochloride hydrate was shown to have axonal protective effects in TNF-induced optic nerve degeneration. The α2-adrenoreceptor agonist brimonidine was also shown to exert axonal protection. The current study aimed to elucidate whether additive axonal protection was achieved by the simultaneous injection of ripasudil and brimonidine and examine the association with AMPK activation. Methods Intravitreal administration was performed in the following groups: PBS, TNF, or TNF with ripasudil, with brimonidine, or with a combination of ripasudil and brimonidine. Axon numbers were counted to evaluate the effects against axon loss. Immunoblot analysis was performed to examine phosphorylated AMPK expression in optic nerves, and immunohistochemical analysis was performed to evaluate the expression levels of p-AMPK and neurofilament in the optic nerve. Results Both ripasudil alone or brimonidine alone resulted in significant neuroprotection against TNF-induced axon loss. The combination of ripasudil and brimonidine showed additive protective effects. Combined ripasudil and brimonidine plus TNF significantly upregulated p-AMPK levels in the optic nerve compared with the TNF groups. Immunohistochemical analysis revealed that p-AMPK is present in axons and enhanced by combination therapy. Conclusion The combination of ripasudil and brimonidine may have additive protective effects compared with single-agent treatment alone. These protective effects may be at least partially associated with AMPK activation.

show abstract

Section: Introductionmentioning

confidence: 99%

Axonal protection by combination of ripasudil and brimonidine with upregulation of p-AMPK in TNF-induced optic nerve degeneration

Otsubo,

Sase,

Tsukahara

et al. 2024

Int Ophthalmol

View full text Add to dashboard Cite

show abstract

“…POAG pathophysiology [ 5 ] determines the state-of-art biomarkers residing in the aqueous humor or the trabecular meshwork, as well as the optic nerve and peripheral blood [ 6 ]. These molecular markers dictate the extracellular matrix status and define cell-signaling or stress molecules and immune surveillance.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Blood B-Cell Subsets Frequency and Distribution and the BSF-2(IL-6) to CSIF:TGIF(IL-10) Ratio as Severity-Associated Signatures in Primary Open-Angle Glaucoma: A Case-Controlled Study

Mokhtar,

Elmadbouly,

Abo Elkheir

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Although primary open-angle glaucoma (POAG) is a major cause of blindness worldwide, patients’ immune response and its relation to the disease course have not been fully unraveled in terms of analyses of circulating B-cell subsets, as well as the association of these subsets with the severity of POAG clinical features. Subjects and Methods: Flow cytometry was used to determine B-cell subset frequencies from 30 POAG patients grouped by hierarchical cluster analysis or the mean deviation (MD) of the visual field (VF) and correlated with the patients’ clinical and pathological data, as well as with BSF-2(IL-6) and CSIF:TGIF(IL-10), which were quantified in peripheral blood samples of patients and controls by ELISA. Results: The total B-cell frequency was increased in the POAG group in comparison to the control group (n = 30). Frequencies of specific B-cell subsets, such as double-negative (DN) and naïve B-cell subsets, were increased in relation to the severity of the POAG disease. However, the unswitched memory B compartment subset decreased in the POAG group. Other non-typical B-cell subsets such as DN B cells also showed significant changes according to the POAG disease severity course. These differences allow us to identify POAG severity-associated inflammatory clusters in patients with specifically altered B-cell subsets. Finally, ocular parameters, biomarkers of inflammation, and other glaucoma-related or non-clinical scores exhibited correlations with some of these B-cell subpopulations. Conclusion: The severity of the POAG disease course is accompanied by changes in the B-cell subpopulation, namely, DN B cells. Furthermore, the existing relationship of the B-cell subset frequencies with the clinical and the inflammatory parameters BSF-2(IL-6), CSIF:TGIF(IL-10), and the BSF-2(IL-6) to CSIF:TGIF(IL-10) ratio suggests that these B lymphocyte cells could serve as potential molecular bio-markers for assessing POAG disease severity and/or progression.

show abstract

Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension

Langbøl,

Saruhanian,

Saruhanian

et al. 2024

Cell Mol Neurobiol

View full text Add to dashboard Cite

Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before (“baseline”), during (“hypoxia”), and after hypoxia (“recovery”). Proteomics based on liquid chromatography coupled with mass spectrometry (LC–MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP. Graphical Abstract

show abstract

New Biomarker Combination Related to Oxidative Stress and Inflammation in Primary Open-Angle Glaucoma

Cited by 6 publications

References 71 publications

Axonal protection by combination of ripasudil and brimonidine with upregulation of p-AMPK in TNF-induced optic nerve degeneration

Axonal protection by combination of ripasudil and brimonidine with upregulation of p-AMPK in TNF-induced optic nerve degeneration

Peripheral Blood B-Cell Subsets Frequency and Distribution and the BSF-2(IL-6) to CSIF:TGIF(IL-10) Ratio as Severity-Associated Signatures in Primary Open-Angle Glaucoma: A Case-Controlled Study

Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension

Contact Info

Product

Resources

About