scholarly journals Hydroquinone increases risk for retinal pigment epithelial (RPE) cell degeneration

2022 ◽  
Vol 100 (S267) ◽  
Author(s):  
Niina Bhattarai ◽  
Maria Hytti ◽  
Yashavanthi Mysore ◽  
Kai Kaarniranta ◽  
Anu Kauppinen
Author(s):  
Shilpi Goenka ◽  
Sanford R. Simon

Smoking is an etiologic factor for age-related macular degeneration (AMD). Although cigarette smoke has been extensively researched for retinal pigment epithelial (RPE) cell degeneration, the potential for adverse effects on the retinal epithelium following exposure to flavored e-cigarette refill liquid has never been explored. In this preliminary study, we have examined the effects of 20 e-liquids (10 different flavored nicotine-free and 10 nicotine-rich e-liquids) used in e-cigarettes on the metabolic activity, membrane integrity, and mitochondrial membrane potential of RPE cells. Our results showed that of the flavors studied over the concentration range: 0.5, 1, and 2% v/v for a duration of 48 h, cinnamon was the most toxic and menthol was the second most toxic, while other flavors showed lesser or no cytotoxicity. The presence of nicotine augmented cytotoxicity for cinnamon, menthol, strawberry, vanilla, and banana while for other flavors there was no synergism. Together, our results demonstrate that exposure of RPE to flavored e-cigarette refill liquids caused significant cytotoxicity and may be a risk factor for the development of retinal pathogenesis, although further in-depth studies are necessary.


2021 ◽  
Vol 22 (15) ◽  
pp. 8130
Author(s):  
Michael H. Guerra ◽  
Thangal Yumnamcha ◽  
Lalit P. Singh ◽  
Ahmed S. Ibrahim

Disruption of retinal pigment epithelial (RPE) barrier integrity is involved in the pathology of several blinding retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR), but the underlying causes and pathophysiology are not completely well-defined. Mitochondria dysfunction has often been considered as a potential candidate implicated in such a process. In this study, we aimed to dissect the role of different mitochondrial components; specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier functionality of RPE. Electric cell-substrate impedance sensing (ECIS) technology was used to collect multi-frequency electrical impedance data to assess in real-time the barrier formation of the RPE cells. For this purpose, the human retinal pigment epithelial cell line—ARPE-19—was used and treated with varying concentrations of specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I (the largest protein complex in the electron transport chain (ETC)); oligomycin for ATP synthase; and carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) for uncoupling ATP synthesis from the accompanying ETC. Furthermore, data were modeled using the ECIS-Zθ software to investigate in depth the effects of these inhibitors on three separate barrier parameters: cell–cell interactions (Rb), cell–matrix interactions (α), and the cell membrane capacitance (Cm). The viability of ARPE-19 cells was determined by lactate dehydrogenase (LDH) Cytotoxicity Assay. The ECIS program’s modeling demonstrated that FCCP and thus OxPhos uncoupling disrupt the barrier function in the ARPE-19 cells across all three components of the total resistance (Rb, α, and Cm) in a dose-dependent manner. On the other hand, oligomycin and thus ATP synthase inhibition mostly affects the ARPE-19 cells' attachment to their substrate evident by a significant decrease in α resistance in a dose-dependent manner, both at the end and throughout the duration of the experiment. On the contrary, rotenone and complex I inhibition mostly affect the ARPE-19 paracellular resistance Rb in a dose-dependent manner compared to basolateral resistance α or Cm. Our results clearly demonstrate differential roles for different mitochondrial components in maintaining RPE cell functionality in which uncoupling of OxPhos is a major contributing factor to the disruption barrier function. Such differences can be used in investigating gene expression as well as for screening of selective agents that improve the OxPhos coupling efficiency to be used in the therapeutic approach for treating RPE-related retinal diseases.


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