Mimicking the ocular environment for the study of inflammatory posterior eye disorders

Dulull, Nabeela K.; Thrimawithana, Thilini; Kwa, Faith A.A.

doi:10.1016/j.drudis.2016.11.012

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…This work warrants future investigations, such as trialling LSF treatment in co-culture models of ARPE-19 and choroid-derived cells, and animal models of AMD. Performing high throughput transcriptomics methods will also help to identify key genes that mediate LSF’s effects on fatty acid and lipid metabolism, biosynthesis and translocation in RPE cells under AMD-like pathological conditions 56 . Other future experiments such Annexin V apoptosis detection and TNF-α assays that can demonstrate LSF’s protection against apoptosis and lipidomic response will also be beneficial.…”

Section: Discussionmentioning

confidence: 99%

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

et al. 2020

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Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients’ quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals. Previously, our laboratory has shown that the vegetable-derived isothiocyanate, L-sulforaphane (LSF), can protect human adult pigment epithelial cells from oxidative damage by upregulating gene expression of the oxidative stress enzyme Glutathione-S-Transferase µ1. This study aims to validate the protective effects of LSF on human retinal cells under oxidative stress conditions and to reveal the key players in fatty acid and lipid metabolism that may facilitate this protection. Methods: The in vitro oxidative stress model of AMD was based on the exposure of an adult retinal pigment epithelium-19 cell line to 200µM hydrogen peroxide. Percentage cell proliferation following LSF treatment was measured using tetrazolium salt-based assays. Untargeted fatty acid profiling was performed by gas chromatography-mass spectrometry. Untargeted lipid profiling was performed by liquid chromatography-mass spectrometry. Results: Under hydrogen peroxide-induced oxidative stress conditions, LSF treatment induced dose-dependent cell proliferation. The key fatty acids that were increased by LSF treatment of the retinal cells include oleic acid and eicosatrienoic acid. LSF treatment also increased levels of the lipid classes phosphatidylcholine, cholesteryl ester and oxo-phytodienoic acid but decreased levels of phosphatidylethanolamine lipids. Conclusions: We propose that retinal cells at risk of oxidative damage and apoptosis can be pre-conditioned with LSF to regulate levels of selected fatty acids and lipids known to be implicated in the pathogenesis and progression of AMD.

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Section: Discussionmentioning

confidence: 99%

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

et al. 2020

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“…Therefore, many pathologies related to the posterior pole of the eye have been associated with these two processes, sharing their pathophysiology not only in oxidative stress but also in inflammation phenomena. Thus, ocular biomarkers associated with oxidative stress and inflammation represent a strategy in the diagnosis and monitoring of ocular diseases [ 4 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

et al. 2021

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Most irreversible blindness observed with glaucoma and retina-related ocular diseases, including age-related macular degeneration and diabetic retinopathy, have their origin in the posterior segment of the eye, making their physiopathology both complex and interconnected. In addition to the age factor, these diseases share the same mechanism disorder based essentially on oxidative stress. In this context, the imbalance between the production of reactive oxygen species (ROS) mainly by mitochondria and their elimination by protective mechanisms leads to chronic inflammation. Oxidative stress and inflammation share a close pathophysiological process, appearing simultaneously and suggesting a relationship between both mechanisms. The biochemical end point of these two biological alarming systems is the release of different biomarkers that can be used in the diagnosis. Furthermore, oxidative stress, initiating in the vulnerable tissue of the posterior segment, is closely related to mitochondrial dysfunction, apoptosis, autophagy dysfunction, and inflammation, which are involved in each disease progression. In this review, we have analyzed (1) the oxidative stress and inflammatory processes in the back of the eye, (2) the importance of biomarkers, detected in systemic or ocular fluids, for the diagnosis of eye diseases based on recent studies, and (3) the treatment of posterior ocular diseases, based on long-term clinical studies.

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Multifunctional nanocomposite eye drops of cyclodextrin complex@layered double hydroxides for relay drug delivery to the posterior segment of the eye

Zhou

et al. 2021

Carbohydrate Polymers

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Mimicking the ocular environment for the study of inflammatory posterior eye disorders

Cited by 7 publications

References 28 publications

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

Multifunctional nanocomposite eye drops of cyclodextrin complex@layered double hydroxides for relay drug delivery to the posterior segment of the eye

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