Role of MMP-9 in Diabetic Retinopathy

Mastari, Ekawaty Suryani; Widjaja, Sry Suryani; Siregar, Yahwardiah; Sari, Mayang

doi:10.22270/jddt.v10i6-s.4635

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…When HRECs were co-cultured with P-ASCs, no evident effects were noted in NG conditions, whereas a strong reduction was observed for VEGF mRNA levels by almost 50%. Since MMP-9 is involved in various mechanisms of DR, such as BRB breakdown, inflammation, neovascularization, and cell apoptosis [ 38 ], we also evaluated its mRNA levels in HRECs in various conditions. In NG medium, neither the presence of ASCs nor that of P-ASCs significantly modified the expression levels of the endopeptidase.…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy

Lupo

Agafonova

Cosentino

et al. 2023

IJMS

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Diabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood–retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs. Based on previous results, the aim of this study was to assess possible beneficial effects exerted by adipose mesenchymal stem cells (ASCs) and their pericyte-like differentiated phenotype (P-ASCs) on human retinal endothelial cells (HRECs) in high glucose conditions (25 mM glucose, HG). P-ASCs were more able to preserve BRB integrity than ASCs in terms of (a) increased transendothelial electrical resistance (TEER); (b) increased expression of adherens junction and tight junction proteins (VE-cadherin and ZO-1); (c) reduction in mRNA levels of inflammatory cytokines TNF-α, IL-1β, and MMP-9; (d) reduction in the angiogenic factor VEGF and in fibrotic TGF-β1. Moreover, P-ASCs counteracted the HG-induced activation of the pro-inflammatory phospho-ERK1/2/phospho-cPLA2/COX-2 pathway. Finally, crosstalk between HRECs and ASCs or P-ASCs based on the PDGF-B/PDGFR-β axis at the mRNA level is described herein. Thus, P-ASCs might be considered valuable candidates for therapeutic approaches aimed at countering BRB disruption in DR.

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Section: Resultsmentioning

confidence: 99%

Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy

Lupo

Agafonova

Cosentino

et al. 2023

IJMS

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“…Выявлено также повышение уровня ММР-9, этот показатель коррелировал с объемом фокальных потерь ГКС и снижением светочувствительности сетчатки. Повышенные уровни ММР-9 в сыворотке крови и/или внутриглазных жидкостях при ДР были выявлены во многих исследованиях, но все они посвящены сосудистым изменениям и диабетическому макулярному отеку [9][10][11]. В литературе отсутствуют данные, определяющие роль MMP-9 в развитии нейродегенерации сетчатки при ДР, однако существуют свидетельства роли ММР-9 в развитии других нейродегенеративных заболеваний, таких как глаукома, болезнь Альцгеймера, болезнь Паркинсона [12].…”

Section: Discussionunclassified

The role of innate immune system mediators in the development of retinal neurodegeneration in type 2 diabetes mellitus

Ruchkin

Просекова

Fedyashev

et al. 2022

Rossijskij oftalʹmologičeskij žurnal

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Purpose. To detect the levels of transform growth factors-β (TGF- β1, TGF- β2, TGF- β3), interferon-ʏ (INF- ʏ), matrix metalloproteinase-9 (MMP-9) and S100B protein in blood serum of patients with type 2 diabetes mellitus (DM) and to reveal the connection of these factors with neurodegenerative changes in the retina. Material and methods. 30 patients, averagely aged 60.3, with type 2 DM and no signs of diabetic retinopathy (DR) (the main group) and 30 healthy individuals (control group) were examined using microperimetry and optical coherence tomography. A sandwich variance estimator of solid phase enzyme-linked immunosorbent assay was used to determine the levels of TGF- β 1, TGF- β2, TGF- β3, INF- ʏ, ММР-9 and S100B protein in blood serum of the subjects examined. Results. The patients with type 2 DM were found to experience an increased level of focal loss of retinal ganglion cells and a drop in the average photosensitivity of the retina. The main group also showed a reliable increase in the level of S100B protein and in the serum level of MMP-9 against the control, but no significant difference between the groups was found in the level of TIMP-1. The level of TGF- β2 was significantly higher in the main group, which also showed a deficiency of TGF- β3. No significant difference was found between the two groups in the levels of TGF- β1 or INF- ʏ. In contrast, a positive correlation was revealed between the levels of S100B, MMP-9 and the volume of focal loss of retinal ganglion cells. Conclusion. Patients with type 2 DM and signs of neurodegeneration of the retina reveal a higher activity of some cytokines and MMP-9. This may indicate an important role of neuroinflammation and dysfunction of the immune system in the retinal neurodegeneration process of DM patients. Further research of other cytokins is required to determine early and more sensitive markers of retinal neurodegeneration.

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Recent Insights into the Etiopathogenesis of Diabetic Retinopathy and Its Management

Biswas,

Choudhury,

Agrawal

et al. 2024

Journal of Ocular Pharmacology and Therapeutics

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Role of MMP-9 in Diabetic Retinopathy

Cited by 3 publications

References 38 publications

Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy

Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy

The role of innate immune system mediators in the development of retinal neurodegeneration in type 2 diabetes mellitus

Recent Insights into the Etiopathogenesis of Diabetic Retinopathy and Its Management

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