Age-related macular degeneration (AMD) holds serious health threats to the elderly population and has a substantial chance leading to permanent loss of vision [1
]. However, there are no effective methods and measures to control or reverse the occurrence of the disease, let alone specific therapeutic drugs. It is, therefore, important to find ways to slow down the pathological changes to delay the progression of the disease [2
]. Although there have been many studies on the pathogenesis and treatment of AMD, its pathogenesis is still unclear. However it is mostly believed to be related with pathological issues like oxidative stress, inflammation and mitochondria dysfunction [3
Ultraviolet (UV) radiation is a risk factor for most kinds of skin and ocular diseases including skin cancer, cataract and AMD. As a part of the light spectrum, UV radiation has a wavelength approximately between 200 and 400 nm. Although the cornea and lens absorb most UVA (320–400nm) and UVB (280–320nm), there is still a small fraction, particularly UVB, reaching the retina. Both the direct irradiation damaging effects to eye tissues and the UV-dependent secondary reactions make UV a main trigger for AMD [4
]. Additionally, oxidative stress remained one of the most destructive secondary reactions of UV radiation. The formed reactive oxygen species (ROS) including singlet oxygen and free radicals, are easily accumulated in polyunsaturated phospholipids within a membrane location in retina [5
]. Notably, macular xanthophylls (MXs), lutein and zeaxanthin (Figure 1
) etc., are also selectively located in the same most vulnerable domains, susceptible to chemical bleaching and act as lipid antioxidants [5
Lots of studies confirmed the impact of high consumption of carotenoids on the lower risks of AMD in the elderly. Carotenoid is one kind of natural essential pigment, which exists in almost all complex or unicellular organisms. For example, MXs also can be produced and collected from marine origin algal and microorganism [7
]. They are presented in human diets as a nutrient enhancer, colorful agent, even medicine [10
]. One of the medical applications of carotenoids is their important role in protecting the eye function. For example, MXs are selectively accumulated in retina to alleviate light damage. In addition to MXs, researches also demonstrated the preventing effects of many other natural pigments on AMD, such as β-carotene, astaxanthin, and anthocyanin [11
]. However, one special carotenoid exists in the human diet, isorenieratene (Figure 1
), whose potential effects on AMD has never been studied.
According to our recent work, Rhodococcus sp. B7740 from the Arctic Ocean can produce amounts of menaquinones and special aromatic carotenoids including isorenieratene [10
]. As hydrocarbon carotenoid, unlike β-carotene with two β rings, isorenieratene has special aromatic structure (two ϕ rings) thus might possess different bio-active functions. Reported data showed that isorenieratene possessed higher stability against oxidation stress than common plant source carotenoids [10
]. In addition, benzene rings could increase its ability of UV resistance [15
]. This provides the foundation for the conception and design of this article. Moreover, the wide research niche of this special marine origin carotenoid made us focus on its potential biologic functions and internal mechanisms.
To investigate the potential effect of isorenieratene in the vulnerable polyunsaturated phospholipid domain, the multilamellar vesicles model using 1-palmitoyl-2-oleoylphosphatidylcholine (POPC, Figure 1
), was applied in our research under UVB radiation [16
]. Meanwhile, electron paramagnetic resonance (EPR) analysis, a sharp method to monitor free radicals, was performed to evaluate the scavenging ROS effects of isorenieratene compared with MXs.
In the mean time, the retinal-pigmented epithelial (RPE) layer, a major ocular tissue, is known to play an important role in the etiology of AMD. Cultured RPE cells exposure to UVB showed multiple cellular pathological features such as the reduced cell viability, increased cell apoptosis, reactive oxygen species (ROS) accumulation and mitochondrial dysfunction [4
]. Thus, in this study, the defense effects of isorenieratene against UV-induced damage upon the ARPE-19 cell model was applied and also compared with MXs. It’s noteworthy that TSPO, an 18 kDa translocator protein, is located on the mitochondrial membrane in the cell. Research showed that TSPO-/-RPE cells possessed a significantly higher amount of ROS, lower cell viabilities and higher cholesterol efflux [19
]. Thus ligands, which could bind with this specific protein, might contribute to the prevention of AMD. Additionally, stimulating over-expression of tspo
in RPE cells by special ligands could be a new pharmacological way to treat early AMD patients. Mages et al. found that the special TSPO ligand XBD173 could protect inner retinal neurons by attenuating the glial response [20
]. However, there is no research talking about the possible effects of MXs or other natural drugs as specific TSPO ligand in the ARPE-19 cell. Based on that, the potential effects of isorenieratene and MXs on ARPE-19 cells in the perspective of tspo
expression were explored. Their special interacting mechanisms as TSPO ligand, were also studied and compared for the first time. Combined results clearly demonstrated the outstanding function of isorenieratene in eye protection. The aim of this study is to explore the potential bio-activity of this special aromatic carotenoid from the Arctic Ocean. We presume this aromatic carotenoid would have a promising application in the field of medicine.