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.
Tremendous progress has been made in the field of toxicology leading to the advance of developmental toxicity assessment. Conventional animal models and in vitro two-dimensional models cannot ...accurately describe toxic effects and predict actual in vivo responses due to obvious inter-species differences between humans and animals, as well as the lack of a physiologically relevant tissue microenvironment. Human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived three-dimensional organoids are ideal complex and multicellular organotypic models, which are indispensable in recapitulating morphogenesis, cellular interactions, and molecular processes of early human organ development. Recently, human organoids have been used for drug discovery, chemical toxicity and safety in vitro assessment. This review discusses the recent advances in the use of human organoid models, (i.e., brain, retinal, cardiac, liver, kidney, lung, and intestinal organoid models) for developmental toxicity and teratogenicity assessment of distinct tissues/organs following exposure to pharmaceutical compounds, heavy metals, persistent organic pollutants, nanomaterials, and ambient air pollutants. Combining next-generation organoid models with innovative engineering technologies generates novel and powerful tools for developmental toxicity and teratogenicity assessment, and the rapid progress in this field is expected to continue.
•Advances in stem cell techniques for toxicity assessment.•Human organoids can decipher the embryonic development and morphogenesis.•Organoid technologies for developmental toxicology assessment.•Advanced next-generation human organoids toward next-level toxicity testing.
Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal ...progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats. We report that HRPCs/HBMSCs combined transplantation maintains the electroretinogram results much better than HRPCs or HBMSCs single transplantations. The thickness of outer nuclear layer also presented a better outcome in the combined transplantation. Importantly, grafted cells in the combination migrated better, both longitudinally and latitudinally, than single transplantation. The photoreceptor differentiation of grafted cells in the retina of RCS rats receiving combined transplantation also showed a higher ratio than single transplantation. Finally, activation of microglia and the gliosis of Müller cells were more effectively suppressed in combined transplantation, indicating better immunomodulatory and anti-gliosis effects. Taken together, combining the transplantation of HRPCs and HBMSCs is a more effective strategy in stem cell-based therapy for retinal degenerative diseases.
Oxidation is an essential factor during cataract development. Autophagy, usually a cytoprotective process, is always found elevated in lens epithelial cells under oxidation, yet its roles and ...associated molecular mechanisms under such circumstances are rarely elucidated. Herein, we extracted and re-analyzed the RNA sequencing data of the GSE161701 dataset from the Gene Expression Omnibus database to identify the differentially expressed mRNAs and lncRNAs by using the R package "DESeq2". Further analyses of gene ontology and KEGG enrichment were implemented
the packages "clusterProfiler" and "enrichplot". We found that after the knockout of
, differentially expressed genes were more associated with hemopoiesis, vasculature development, axonogenesis, and hypoxia regulation. When stimulated with H
O
, LECs displayed a gene expression profile correlating with apoptotic and proliferative pathways, such as the MAPK signaling pathway and FoxO signaling pathway. The differentially expressed gene profiles of the two types of LECs (wild type and ATG7 deficient) under oxidation were distinct to a large extent. Furthermore, 1,341 up-regulated and 1912 down-regulated differential mRNAs and 263 up-regulated and 336 down-regulated differential lncRNAs between these two types of LECs subjected to H
O
were detected, among which 292 mRNAs and 24 lncRNAs possibly interacted with ten cataract-related miRNAs. A competing endogenous lncRNA-miRNA-mRNA network based on such interactions was finally constructed.
Retinal degenerative disease (RDD) refers to a group of diseases with retinal degeneration that cause vision loss and affect people's daily lives. Various therapies have been proposed, among which ...stem cell therapy (SCT) holds great promise for the treatment of RDDs. Microglia are immune cells in the retina that have two activation phenotypes, namely, pro-inflammatory M1 and anti-inflammatory M2 phenotypes. These cells play an important role in the pathological progression of RDDs, especially in terms of retinal inflammation. Recent studies have extensively investigated the therapeutic potential of stem cell therapy in treating RDDs, including the immunomodulatory effects targeting microglia. In this review, we substantially summarized the characteristics of RDDs and microglia, discussed the microglial changes and phenotypic transformation of M1 microglia to M2 microglia after SCT, and proposed future directions for SCT in treating RDDs.
Retinal vein occlusion (RVO) is a common retinal venous disorder that causes vision loss. No specific therapy has been developed. Controversy exists regarding two treatments: intravitreal ...dexamethasone implants and anti-vascular endothelial growth factor (VEGF). The goal of this study is to compare the effectiveness and safety of dexamethasone implants and anti-VEGF treatment for RVO.
The PubMed, Embase, and Cochrane Library databases were searched for studies comparing dexamethasone implants with anti-VEGF in patients with RVO. Best-corrected visual acuity (BCVA), central subfield thickness (CST), intraocular pressure changes, conjunctival haemorrhage, reduced VA, and macular oedema were extracted from the final included studies. RevMan 5.3 was used to conduct the quantitative analysis and bias assessment.
Four randomised controlled trials assessing 969 eyes were included. The anti-VEGF treatment showed better BCVA improvement (mean difference MD = - 10.59, P < 0.00001) and more CST decrease (MD = - 86.71 μm, P = 0.02) than the dexamethasone implants. However, the dexamethasone implants required fewer injections. As for adverse effects, the dexamethasone implants showed significantly higher intraocular pressure (IOP) and more cataracts than the anti-VEGF treatment. No significant differences were found in conjunctival haemorrhage, reduced VA, and macular oedema.
Anti-VEGF treatment showed better functional and anatomical improvement with less risk of IOP elevation and cataract formation compared to dexamethasone implants. Thus, anti-VEGF treatment is the first choice for treating RVO patients.
Retinal degenerative diseases (RDDs) are the leading causes of blindness and currently lack effective treatment. Cytotherapy has become a promising strategy for RDDs. The transplantation of olfactory ...ensheathing cells (OECs) or neural stem cells (NSCs) has recently been applied for the experimental treatment of RDDs. However, the long-term outcomes of single-cell transplantation are poor. The combined transplantation of multiple types of cells might achieve better effects. In the present study, OECs containing olfactory nerve fibroblasts (ONFs) and NSCs were cotransplanted into the subretinal space of Royal College of Surgeons (RCS) rats. Using electroretinogram (ERG), immunofluorescence, Western blot, and
Transwell system, the differences in the electrophysiological and morphological changes of single and combined transplantation as well as the underlying mechanisms were explored at 4, 8, and 12 weeks postoperation. In addition, using the Transwell system, the influence of OECs on the stemness of NSCs was discovered. Results showed that, compared to the single transplantation of OECs or NSCs, the combined transplantation of OECs and NSCs produced greater improvements in b-wave amplitudes in ERGs and the thickness of the outer nuclear layer at all three time points. More endogenous stem cells were found within the retina after combined transplantation. Glial fibrillary acidic protein (GFAP) expression decreased significantly when NSCs were cotransplanted with OECs. Both the vertical and horizontal migration of grafted cells were enhanced in the combined transplantation group. Meanwhile, the stemness of NSCs was also better maintained after coculture with OECs. Taken together, the results suggested that the combined transplantation of NSCs and OECs enhanced the improvement in retinal protection in RCS rats, providing a new strategy to treat RDDs in the future.
A 59‐year‐old patient presented with 4‐day acute painless bilateral visual loss, MRI results showed dura enhancement of the frontal, anterior cranial fossa. The patient was considered to have ...idiopathic hypertrophic cranial pachymeningitis based on laboratory tests and MRI data. After treatment with hormones, the visual acuity obviously improved.
We reported a patient presented with 4‐day acute painless bilateral visual loss, who was diagnosed to have idiopathic hypertrophic cranial pachymeningitis based on laboratory tests and MRI data, the visual acuity obviously improved after timely treatment. Therefore, Intracranial changes should be considered in patients with a sharp decline in visual acuity but with no obviously positive signs of the eye fundus.
Background/Aims: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown ...neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.
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.
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