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Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects and mitigates retinal pigment epithelium (RPE) cell damage caused by blue-light exposure. We investigated whether KW3110 suppresses chronic inflammatory stress-induced RPE cell damage by modulating immune cell activity and whether it improves ocular disorders in healthy humans. First, we showed that KW3110 treatment of mouse macrophages (J774A.1) produced significantly higher levels of interleukin-10 as compared with other lactic acid bacterium strains (all p < 0.01). Transferring supernatant from KW3110- and E. coli 0111:B4 strain and adenosine 5′-triphosphate (LPS/ATP)-stimulated J774A.1 cells to human retinal pigment epithelium (ARPE-19) cells suppressed senescence-associated phenotypes, including proliferation arrest, abnormal appearance, cell cycle arrest, and upregulation of cytokines, and also suppressed expression of tight junction molecule claudin-1. A randomized, double-blind, placebo-controlled parallel-group study of healthy subjects (n = 88; 35 to below 50 years) ingesting placebo or KW3110-containing supplements for 8 weeks showed that changes in critical flicker frequency, an indicator of eye fatigue, from the week-0 value were significantly larger in the KW3110 group at weeks 4 (p = 0.040) and 8 (p = 0.036). These results suggest that KW3110 protects ARPE-19 cells against premature senescence and aberrant expression of tight junction molecules caused by chronic inflammatory stress, and may improve chronic eye disorders including eye fatigue.

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride intracellular channel 4 (CLIC4) is a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit a full spectrum of functional and pathological hallmarks of dry AMD. Multidisciplinary longitudinal studies of disease progression in these mice support a mechanistic model that links RPE cell-autonomous aberrant lipid metabolism and transport to drusen formation. Age-related macular degeneration (AMD) is a leading cause of blindness and is characterised by the accumulation of lipid deposits, called drusen. Here, the authors show that mice lacking chloride intracellular channel 4 in retinal pigment epithelium have defective lipid processing in the eye and pathological features mirroring human AMD, including drusen formation.

An engineered patch of retinal pigment epithelium generated from human embryonic stem cells is transplanted into the eyes of two patients. Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)–derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD.

Anthocyanins are polyphenol compounds that render various hues of pink, red, purple, and blue in flowers, vegetables, and fruits. Anthocyanins also play significant roles in plant propagation, ecophysiology, and plant defense mechanisms. Structurally, anthocyanins are anthocyanidins modified by sugars and acyl acids. Anthocyanin colors are susceptible to pH, light, temperatures, and metal ions. The stability of anthocyanins is controlled by various factors, including inter and intramolecular complexations. Chromatographic and spectrometric methods have been extensively used for the extraction, isolation, and identification of anthocyanins. Anthocyanins play a major role in the pharmaceutical; nutraceutical; and food coloring, flavoring, and preserving industries. Research in these areas has not satisfied the urge for natural and sustainable colors and supplemental products. The lability of anthocyanins under various formulated conditions is the primary reason for this delay. New gene editing technologies to modify anthocyanin structures in vivo and the structural modification of anthocyanin via semi-synthetic methods offer new opportunities in this area. This review focusses on the biogenetics of anthocyanins; their colors, structural modifications, and stability; their various applications in human health and welfare; and advances in the field.

Microalgae productive chains are gaining importance as sustainable alternatives to obtain natural pigments. This work presents a review on the most promising pigments and microalgal sources by gathering trends from a 10-year bibliometric survey, a patents search, and an industrial and market analysis built from available market reports, projects and companies’ webpages. The performed analysis pointed out chlorophylls, phycocyanin, astaxanthin, and β-carotene as the most relevant pigments, and Chlorella vulgaris, Spirulina platensis, Haematococcus pluvialis, and Dunaliella salina, respectively, as the most studied sources. Haematococcus is referred in the highest number of patents, corroborating a high technological interest in this microalga. The biorefinery concept, investment in projects and companies related to microalgae cultivation and/or pigment extraction is increasingly growing, particularly, for phycocyanin from Spirulina platensis. These pieces of evidence are a step forward to consolidate the microalgal pigments market, which is expected to grow in the coming years, increasing the prospects of replacing synthetic pigments by natural counterparts.

Some of the most important natural pigments have been produced from fungi and used for coloring in food, cosmetics, textiles, and pharmaceutical products. Forty-seven isolates of endophytic fungi were isolated from Cinnamomum zeylanicum in northern Thailand. Only one isolate, CMU-ZY2045, produced an extracellularly red pigment. This isolate was identified as Nigrospora aurantiaca based on morphological characteristics and the molecular phylogenetic analysis of a combined four loci (large subunit and internal transcribed spacer of ribosomal DNA, β-tubulin, and translation elongation factor 1-alpha genes). The optimum conditions for red pigment production from this fungus were investigated. The results indicated that the highest red pigment yield was observed in the liquid medium containing glucose as a carbon source and yeast extract as a nitrogen source, at a pH value of 5.0 and at 27 °C with shaking for 5 days. The crude red pigment revealed the highest level of solubility in methanol. A fungal red pigment was found to have high stability at temperatures ranging from 20 to 50 °C and pH values at a range of 5.0–6.0. Based on liquid chromatography-mass spectrometry analyses, the red pigment was characterized as bostrycin. The extracted pigment was used for the textile dyeing process. Crude fungal red pigment revealed the highest staining ability in cotton fabrics and displayed excellent fastness to washing, which showing negative cytotoxicity at the concentrations used to cell culture. This is the first report on bostrycin production from N. aurantiaca .

Tissue homeostasis emerges from mechanical feedback loops balanced by cell loss and proliferation, a balance that in postmitotic tissues must be maintained without compensatory proliferation. Yet how these tissues preserve mechanical homeostasis and how this challenges function in ageing remains unclear. To establish the relationship between cell density, mechanical homeostasis, and function, we induced age-mimicking cell loss in a postmitotic retinal pigment epithelium (RPE) in vitro. This model recapitulates key structural hallmarks of RPE ageing, including reduced cell height, shortened microvilli and cytoskeletal reorganisation. The density-reduced RPE establishes a new mechanical equilibrium characterised by tissue stiffening and increased junctional contractility. Functionally, these monolayers exhibit impaired phagocytosis of photoreceptor outer segments due to compromised apicolateral plasticity, which is mechanistically linked to the modulation of actin nucleators, Arp2/3 and formins. Altogether, our findings show that a cell loss-induced shift in mechanical homeostasis drives age-related RPE dysfunction, demonstrating that structural remodelling and mechanics alone can compromise tissue function in ageing. Age-related cell loss in the retinal pigment epithelium triggers structural and mechanical remodelling that compromises vision-supporting phagocytosis. This study shows that altered mechanical homeostasis alone can drive functional decline in ageing tissue.

The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.