Disruption of retinal pigment epithelial cell properties under the exposure of cotinine

Abstract

Cigarette smoking is a major risk factor for age-related macular degeneration (AMD), in which progressive retinal pigment epithelial (RPE) cell degeneration is a major pathological change. Nicotine is a major biologically active component in cigarette smoke. It is continuously catabolized into cotinine, which has longer half-life and higher concentration in tissue cells and fluids. Here we hypothesized that continuous exposure of cotinine has more potent effects on human RPE cell properties than nicotine. Human RPE cell line (ARPE-19) was treated continuously with 1–2 µM of nicotine and/or cotinine for 7 days. RPE cells treated with 2 μM cotinine and nicotine-cotinine mixture has lower MTT signals without significant changes in cell apoptosis or integrity. Moreover, RPE cell migration was retarded under cotinine treatments, but not nicotine. Both nicotine and cotinine treatments attenuated the phagocytotic activity of RPE cells. In addition, cotinine and nicotine-cotinine mixture suppressed VEGF and IL-8 expression and upregulated TIMP-2 expression. Expressions of autophagy genes were upregulated by the cotinine treatment, whereas expressions of epithelial-to-mesenchymal transition markers were downregulated. In conclusion, our study, for the first time, demonstrated that cotinine, rather than nicotine, affects the properties of RPE cells in vitro, which could explain the smoking-induced RPE pathology.

Factors affecting resolution of subretinal fluid after selective retina therapy for central serous chorioretinopathy

“…Smoking is not only associated with developing CSC, but poor visual prognosis and longer treatment needed in CSC patients 41 . Cotinine, the major nicotine metabolite, reduces RPE cell repair, wound healing ability and phagocytotic activity in vitro 42 . Fujihara et al reported that chronic cigarette smoke develops evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch's membrane, and RPE cell apoptosis 43 .…”

Expression of SARS-CoV-2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea

“…Human ocular cell lines, including retinal pigment epithelial (RPE) cells ARPE-19 (catalogue number: CRL-2302, American Type Culture Collection (ATCC), Manassas, VA) [11,12], lens epithelial cells B3 (catalogue number: CRL-11421, ATCC) [13], primary trabecular meshwork (TM) cells [14], and retinoblastoma cells Y79 (catalogue number: HTB-18, ATCC) [15], have been previously established. We also collected human mesenchymal stem cells (MSCs) from different sources, including bone marrow-derived MSCs (BM-MSCs; catalogue number: 7500; ScienceCell Research Laboratories, Carlsbad, CA) [16], adipose-derived stem cells (ASCs) [17], and periodontal ligament-derived stem cells (PDLSCs) [18,19].…”

Factors Affecting Resolution of Subretinal Fluid After Selective Retina Therapy for Central Serous Chorioretinopathy

“…Smoking is not only associated with developing CSC, but poor visual prognosis and longer treatment needed in CSC patients [33]. Cotinine, the major nicotine metabolite, reduces RPE cell repair, wound healing ability and phagocytotic activity in vitro [34]. Fujihara et al reported that chronic cigarette smoke develops evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch membrane, and RPE cell apoptosis [35].…”