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Fibrotic cataracts, including anterior subcapsular cataract (ASC) as well as posterior capsule opacification (PCO), are a common vision-threatening cause worldwide. Still, little is known about the underlying mechanisms. Here, we demonstrate a miRNA-based pathway regulating the pathological fibrosis process of lens epithelium. Gain- and loss-of-function approaches, as well as multiple fibrosis models of the lens, were applied to validate the crucial role of two miR-1225 family members in the TGF-β2 induced PCO model of human LECs and injury-induced ASC model in mice. Both miR-1225-3p and miR-1225-5p prominently stimulate the migration and EMT process of lens epithelial cells (LECs) in vitro as well as lens fibrosis in vivo. Moreover, we demonstrated that the underlying mechanism for these effects of miR-1225-5p is via directly targeting Keap1 to regulate Keap1/Nrf2 signaling. In addition, evidence showed that Keap1/Nrf2 signaling is activated in the TGF-β2 induced PCO model of human LECs and injury-induced ASC model in mice, and inhibition of the Nrf2 pathway can significantly reverse the process of LECs EMT as well as lens fibrosis. These results suggest that blockade of miR-1225-5p prevents lens fibrosis via targeting Keap1 thereby inhibiting Nrf2 activation. The 'miR-1225-Keap1-Nrf2' signaling axis presumably holds therapeutic promise in the treatment of fibrotic cataracts. [ABSTRACT FROM AUTHOR]

Thanks to progress in the development of three‐dimensional (3D) culture technologies, human central nervous system (CNS) development and diseases have been gradually deciphered by using organoids derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). Selforganized neural organoids (NOs) have been used to mimic morphogenesis and functions of specific organs in vitro. Many NOs have been reproduced in vitro, such as those mimicking the human brain, retina, and spinal cord. However, NOs fail to capitulate to the maturation and complexity of in vivo neural tissues. The persistent issues with current NO cultivation protocols are inadequate oxygen supply and nutrient diffusion due to the absence of vascular networks. In vivo, the developing CNS is interpenetrated by vasculature that not only supplies oxygen and nutrients but also provides a structural template for neuronal growth. To address these deficiencies, recent studies have begun to couple NO culture with bioengineering techniques and methodologies, including genetic engineering, coculture, multidifferentiation, microfluidics and 3D bioprinting, and transplantation, which might promote NO maturation and create more functional NOs. These cutting‐edge methods could generate an ever more reliable NO model in vitro for deciphering the codes of human CNS development, disease progression, and translational application. In this review, we will summarize recent technological advances in culture strategies to generate vascularized NOs (vNOs), with a special focus on cerebral‐ and retinal‐organoid models. [ABSTRACT FROM AUTHOR]

In order to investigate quantitatively the influence of multiple aggregate factors on the interfacial transition zone (ITZ) and to determine the major and minor factors, it is necessary to adopt a mathematic model. A mathematic model of the interface influence factor ( ) is proposed, based on a previous formula of the volume fraction of the ITZ and combined with microhardness test results. Using the model, the positive and negative influences on the ITZ of coarse aggregate of different types, volume fractions and grading can be quantitatively assessed. Furthermore, the grey correlation degree between the coarse aggregate and is analysed. The results show that, for normal weight aggregate (NWA), the aggregate grading is the major influencing factor and, for lightweight aggregate (LWA), water absorption is the major influencing factor; both of these factors have the highest correlation degree with . Therefore, to improve the microstructure of the ITZ in concrete, NWA with a large average particle size and LWA with a high water absorption should be used to prepare the concrete, on the premise of meeting the necessary workability and mechanical properties of the concrete. The grey correlation model can be successfully applied to sensitivity analysis of the influence of coarse aggregate with various factors on the ITZ. [ABSTRACT FROM AUTHOR]

Stem cell therapy may replace lost photoreceptors and preserve residual photoreceptors during retinal degeneration (RD). Unfortunately, the degenerative microenvironment compromises the fate of grafted cells, demanding supplementary strategies for microenvironment regulation. Donor cells with both proper regeneration capability and intrinsic ability to improve microenvironment are highly desired. Here, we use cell surface markers (C-Kit+/SSEA4−) to effectively eliminate tumorigenic embryonic cells and enrich retinal progenitor cells (RPCs) from human embryonic stem cell (hESC)-derived retinal organoids, which, following subretinal transplantation into RD models of rats and mice, significantly improve vision and preserve the retinal structure. We characterize the pattern of integration and materials transfer following transplantation, which likely contribute to the rescued photoreceptors. Moreover, C-Kit+/SSEA4− cells suppress microglial activation, gliosis and the production of inflammatory mediators, thereby providing a healthier host microenvironment for the grafted cells and delaying RD. Therefore, C-Kit+/SSEA4− cells from hESC-derived retinal organoids are a promising therapeutic cell source. Stem cell transplantation to treat retinal degeneration could be limited by the degenerative microenvironment. Here, the authors show that C-Kit+/SSEA4- progenitor cells enriched from human embryonic stem cell derived retinal organoids protect retinal structure, suppress microglial activation, gliosis and inflammation. [ABSTRACT FROM AUTHOR]

Posterior capsule opacification (PCO) is one of the most frequent late-onset complications after cataract surgery. Several kinds of drug-eluting intraocular lenses (IOL) were designed for sustainable drug release to suppress ocular inflammation, the proliferation of lens epithelial cells (LECs) and the development of PCO after cataract surgery. Despite previous advances in this field, the drug-loaded IOLs were limited in ocular toxicity, insufficient drug-loading capacity, and short release time. To prevent PCO and to address these drawbacks, a novel drug-loaded IOL (Rapa@Ti 3 C 2 -IOL), prepared from two-dimensional ultrathin Ti 3 C 2 MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti 3 C 2 was prepared via electrostatic self-assembly of Ti 3 C 2 and Rapa, with a loading capacity of Rapa at 92%. Ti 3 C 2 was used as a drug delivery reservoir of Rapa. Rapa@Ti 3 C 2 -IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti 3 C 2 -IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti 3 C 2 coating effectively eliminated the LECs around Rapa@Ti 3 C 2 -IOL under a mild 808-nm NIR laser irradiation (1.0 W/cm -2 ). Moreover, NIR-controllable Rapa release inhibited the migration of LECs and suppressed the inflammatory response after photothermal therapy in vitro. Then, Rapa@Ti 3 C 2 -IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti 3 C 2 -IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and no obvious pathological damage was observed in surrounding healthy tissues. In summary, the present study offers a promising strategy for preventing PCO via ultrathin Ti 3 C 2 MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties., (Copyright © 2022 Ye, Huang, Li, Ma, Gao, Hu, He, Jin and Li.)