Retinal neuroinflammatory induced neuronal degeneration - Role of toll-like receptor-4 and relationship with gliosis

Ghosh, Fredrik; Abdshill, Hodan; Arnér, Karin; Voss, Ulrikke; Taylor, Linnéa

doi:10.1016/j.exer.2018.02.002

Cited by 17 publications

(10 citation statements)

References 31 publications

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“…Galectin-3 is a protein with several essential functions for physiological, as well as pathological processes including macrophage activation, fibrosis, apoptosis, cell-cell adhesion, and cell-matrix interaction [28]. To our knowledge, galectin-3 upregulation after vitrectomy has not been previously described, and this phenomenon may indicate a neuroinflammatory response within the retina that is separate from gliosis [44]. Immune responses following vitrectomy were not, however, limited to retina-intrinsic reactions.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model

Barth

Crafoord

Arnér

et al. 2019

Graefes Arch Clin Exp Ophthalmol

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Purpose To investigate the inflammatory response of current and future potential vitreous substitutes in an experimental in vivo vitrectomy model. Methods Twenty-five gauge pars plana vitrectomy was performed in the right eye of 60 pigmented rabbits, with subsequent injection of 0.5-1.0 ml of Healaflow® (cross-linked hyaluronic acid, n = 12), Bio-Alcamid® (polyalkylimide, n = 8), silicone oil (n = 12), or balanced saline solution (BSS, n = 28). Postoperative clinical evaluation was performed; and the rabbits were sacrificed at 1 day, 1 week, or 1 month. The eyecups were then examined macroscopically; the retinas sectioned and stained with hematoxylin and eosin (Htx), and immunohistochemically labeled for glial fibrillary acidic protein (GFAP), CD45, galectin-3, CD68, and CD20. Unoperated left eyes from treated animals as well as eyes from untreated animals were used as controls. Results Vitrectomy without major complications was achieved in 46/60 eyes. The remaining 14 eyes were analyzed separately. One eye developed endophthalmitis after 1 week and was excluded. Eyes treated with Healaflow®, silicone oil, and BSS had a comparable appearance macroscopically and in Htx-stained sections, whereas Bio-Alcamid®-injected eyes exhibited increased macroscopic inflammation and severely affected retinas. GFAP upregulation was present in all treatment groups, most prominent in eyes treated with Bio-Alcamid® and silicone oil. Upregulation of CD45 and CD68 in the inner retina and vitreous space was most prominent with Bio-Alcamid® treatment, and these eyes together with their silicone oil-treated counterparts also displayed a stronger upregulation of CD20-labeled cells compared with remaining groups. General upregulation of galectin-3, mainly in the inner retina, was found in all groups. In eyes with perioperative complications, labeling of CD45, CD68, and especially GFAP was comparably high. Conclusions We here describe differences in the postsurgery inflammatory profiles of existing and potential vitreous substitutes. Bio-Alcamid® and silicone oil display severe signs of gliosis and inflammation, whereas Healaflow® elicits minimal reactions comparable with BSS, highlighting its potential application as a vitreous substitute in a future clinical setting.

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Section: Discussionmentioning

confidence: 99%

Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model

Barth

Crafoord

Arnér

et al. 2019

Graefes Arch Clin Exp Ophthalmol

Self Cite

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“…However, this effect is restrained by relatively low LPS activity and intact host immunity at the very early stages of DM. In contrast, there is persistently high-level serum LPS combined with impaired immunity at the advanced stages [ 22 ], thus circulating LPS can play a significant part in the progression of DR. By disturbing ocular homeostasis, intruding LPS activate a wide variety of retinal cells to intensify the retinal inflammatory cascades as well as cell degeneration [ 57 , 64 , 80 – 88 ], which manifests as aggravation of BRB dysfunction, reduction of retinal blood perfusion, and deterioration of neural dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Activated caspase-1 further hydrolyses pro-IL-1β and pro-IL-18 to intensify inflammation [ 56 ]. Of note, TLRs and NLRs are widely expressed on retinal cells, and pharmacological blockade of these receptors strongly ameliorates the retinal pathology induced by LPS [ 57 , 58 ].…”

Section: Possible Mechanisms Of Lps In the Pathogenesis Of Drmentioning

confidence: 99%

The role of lipopolysaccharides in diabetic retinopathy

Qin

Zou

2022

BMC Ophthalmol

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Diabetes mellitus (DM) is a complex metabolic syndrome characterized by hyperglycemia. Diabetic retinopathy (DR) is the most common complication of DM and the leading cause of blindness in the working-age population of the Western world. Lipopolysaccharides (LPS) is an essential ingredient of the outer membrane of gram-negative bacteria, which induces systemic inflammatory responses and cellular apoptotic changes in the host. High-level serum LPS has been found in diabetic patients at the advanced stages, which is mainly due to gut leakage and dysbiosis. In this light, increasing evidence points to a strong correlation between systemic LPS challenge and the progression of DR. Although the underlying molecular mechanisms have not been fully elucidated yet, LPS-related pathobiological events in the retina may contribute to the exacerbation of vasculopathy and neurodegeneration in DR. In this review, we focus on the involvement of LPS in the progression of DR, with emphasis on the blood-retina barrier dysfunction and dysregulated glial activation. Eventually, we summarize the recent advances in the therapeutic strategies for antagonising LPS activity, which may be introduced to DR treatment with promising clinical value.

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“…A pre-clinical study indicated that systemically administered MSCs did not migrate to the injured eyes and had no effects on RDDs, as they are trapped in lung capillary beds (Johnson et al, 2010;Ge et al, 2014). Thus, local administration is the major route of delivery of MSCs for RDD therapy, as this route can deliver paracrine factors directly to the retina.…”

Section: Optimization Of Delivery Methodsmentioning

confidence: 99%

“…In addition, diabetic retinopathy (DR), glaucoma, and some other retinopathies can damage the retinal neurons and are thus also considered RDDs (Gorbatyuk and Gorbatyuk, 2013;Mead et al, 2015). These diseases primarily damage the ganglion cells (RGCs), photoreceptors (rods and cones), or retinal pigment epithelium (RPE) cells (Mead et al, 2015) but can also induce some secondary cellular reactions such as neuro-inflammation, microglial activation, and retinal gliosis (activation of the Müller glial cells) (Ghosh et al, 2018;Rashid et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Interaction Between Mesenchymal Stem Cells and Retinal Degenerative Microenvironment

et al. 2021

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Retinal degenerative diseases (RDDs) are a group of diseases contributing to irreversible vision loss with yet limited therapies. Stem cell-based therapy is a promising novel therapeutic approach in RDD treatment. Mesenchymal stromal/stem cells (MSCs) have emerged as a leading cell source due to their neurotrophic and immunomodulatory capabilities, limited ethical concerns, and low risk of tumor formation. Several pre-clinical studies have shown that MSCs have the potential to delay retinal degeneration, and recent clinical trials have demonstrated promising safety profiles for the application of MSCs in retinal disease. However, some of the clinical-stage MSC therapies have been unable to meet primary efficacy end points, and severe side effects were reported in some retinal “stem cell” clinics. In this review, we provide an update of the interaction between MSCs and the RDD microenvironment and discuss how to balance the therapeutic potential and safety concerns of MSCs' ocular application.

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Retinal neuroinflammatory induced neuronal degeneration - Role of toll-like receptor-4 and relationship with gliosis

Cited by 17 publications

References 31 publications

Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model

Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model

The role of lipopolysaccharides in diabetic retinopathy

Interaction Between Mesenchymal Stem Cells and Retinal Degenerative Microenvironment

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