Abstract
Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.
Highlights
Age-related macular degeneration (AMD) is a degenerative macular disease that causes vision loss in the aged population [1]
To investigate the effect of adding oAβ1-42 in ARPE-19 cells, the Aβ peptide was incubated at 37 ◦ C for 24 h, and the presence of the oligomeric form was further confirmed by immunocytochemistry staining of A11 or Aβ oligomer markers (Figure 1A)
The compound 4-(phenylsulfanyl) butan2-one (4-PSB-2) can effectively suppress overexpression of tumor necrosis factor-α (TNF-α), COX-2, and inducible nitric oxide synthase (iNOS) via NF-κB signaling in ARPE-19 cells induced by pression of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells induced by oAβ1-42 treatment without causing any notable side effects (Figure 5)
Summary
Age-related macular degeneration (AMD) is a degenerative macular disease that causes vision loss in the aged population [1]. The dry-type AMD shows slower progression than wet-type AMD, and it affects approximately 80–90% of AMD patients. It is associated with the formation of drusen [4]. Increased size and number of drusen contribute to a higher risk of AMD development and are related to retinal pigment epithelium (RPE) dysfunction, RPE atrophy, and photoreceptor degeneration [5,6]. The amyloidbeta (Aβ) aggregates existing in drusen are related to increased secretion of inflammatory cytokines from RPE cells [9]
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