Pharmacology of the retinal pigment epithelium, the interface between retina and body system

Strauß, Olaf

doi:10.1016/j.ejphar.2016.03.066

Cited by 30 publications

(21 citation statements)

References 181 publications

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“…The retinal pigment epithelium (RPE) is an essential monolayer of pigmented cells of the retina, whose functions include the recycling of rhodopsin chromophores, nourishment of photoreceptors, phagocytosis of the photoreceptor outer segment, and formation of the retinal-blood barrier [ 67 , 68 ]. The RPE cells in healthy adult eyes, similar to other neurons in the human body, are postmitotic in situ [ 69 ], and, hence, maintenance of RPE homeostasis is crucial for effective retinal function.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Abokyi

Shan

et al. 2020

Oxidative Medicine and Cellular Longevity

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Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 ̶ expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.

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Section: Discussionmentioning

confidence: 99%

Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Abokyi

Shan

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…It is worth noting that systemic Ang II reduces RPE renin production via stimulating AT1R and that systematic application of ACE inhibitors strongly activates local RAS in the retina, indicating that the systemic treatment with RAS blockade for retinal degeneration and systemic disease may cause side effects detrimental, or perhaps beneficial, to retinal disease (Strauß 2016) via affecting retinal RAS.…”

Section: Renin Angiotensin System (Ras) and Diabetic Retinopathymentioning

confidence: 99%

Roles of Drug Transporters in Blood-Retinal Barrier

Liu

2019

Advances in Experimental Medicine and Biology

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Blood-retinal barrier (BRB) includes inner BRB (iBRB) and outer BRB (oBRB), which are formed by retinal capillary endothelial (RCEC) cells and by retinal pigment epithelial (RPE) cells in collaboration with Bruch's membrane and the choriocapillaris, respectively. Functions of the BRB are to regulate fluids and molecular movement between the ocular vascular beds and retinal tissues and to prevent leakage of macromolecules and other potentially harmful agents into the retina, keeping the microenvironment of the retina and retinal neurons. These functions are mainly attributed to absent fenestrations of RCECs, tight junctions, expression of a great diversity of transporters, and coverage of pericytes and glial cells. BRB existence also becomes a reason that systemic administration for some drugs is not suitable for the treatment of retinal diseases. Some diseases (such as diabetes and ischemia-reperfusion) impair BRB function via altering tight junctions, RCEC death, and transporter expression. This chapter will illustrate function of BRB, expressions and functions of these transporters, and their clinical significances.

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“…The retinal pigment epithelium (RPE), a monolayer of pigmented cells located between vessels of the choriocapillaris and light-sensitive outer segments of the photoreceptors, is a critical layer that provides trophic support to the photoreceptors [ 1 , 2 ]. It is therefore not surprising that RPE integrity is important for health and functionality of the choroid and retina, as well as the dysfunction and atrophy of the RPE are common pathological characteristics of various degenerative ocular pathologies [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis

et al. 2020

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The oxidative damage of the retinal pigment epithelium (RPE) is the early event that underlies the pathogenesis of maculopathies. Numerous studies have shown that punicalagin (PUN), a polyphenol present in pomegranate, can protect several cell types from oxidative stress. Our study aims to establish if PUN protects RPE from UV radiation-induced oxidative damage. We used an experimental model which involves the use of a human-RPE cell line (ARPE-19) exposed to UV-A radiation for 1, 3, and 5 h. ARPE-19 cells were pre-treated with PUN (24 h) followed by UV-A irradiation; controls were treated identically, except for UV-A. Effects of pre-treatment with PUN on cell viability, intracellular reactive oxygen species ROS levels, modulation of Nrf2 and its antioxidant target genes, and finally apoptosis were examined. We found that pre-treatment with PUN: (1) antagonized the decrease in cell viability and reduced high levels of ROS associated with UV-A-induced oxidative stress; (2) activated Nrf2 signaling pathway by promoting Nrf2 nuclear translocation and upregulating its downstream antioxidant target genes (HO-1 and NQO1); (3) induced an anti-apoptotic effect by decreasing Bax/Bcl-2 ratio. These findings provide the first evidence that PUN can prevent UV-A-induced oxidative damage in RPE, offering itself as a possible antioxidant agent capable of contrasting degenerative eye diseases.

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Pharmacology of the retinal pigment epithelium, the interface between retina and body system

Cited by 30 publications

References 181 publications

Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells

Roles of Drug Transporters in Blood-Retinal Barrier

Punicalagin Protects Human Retinal Pigment Epithelium Cells from Ultraviolet Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signaling Pathway and Reducing Apoptosis

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