Toward the next generation of vascularized human neural organoids.

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.

Impacts of autophagy on the formation of organelle-free zone during the lens development.

The thorough degeneration of organelles in the core of the lens is certainly a hallmark event during the lens development. Organelles degradation in the terminal differentiation process of lens fiber cells to form an organelle-free zone is critical for lens maturation and transparency. Several mechanisms have been proposed to expand our understanding of lens organelles degradation, including apoptotic pathways, the participation of ribozyme, proteolytic enzyme and phospholipase A and acyltransferase, and the newly discovered roles for autophagy. Autophagy is a lysosome-dependent degradation reaction during which the "useless" cellular components are degraded and recycled. These cellular components, such as incorrectly folded proteins, damaged organelles and other macromolecules, are first engulfed by the autophagosome before being further delivered to lysosomes for degradation. Although autophagy has been recognized involving in organelle degradation of the lens, the detailed functions remain to be discovered. Recent advances have revealed that autophagy not only plays a vital role in the intracellular quality control of the lens but is also involved in the degradation of nonnuclear organelles in the process of lens fiber cell differentiation. Herein, we first review the potential mechanisms of organelle-free zone formation, then discuss the roles of autophagy in intracellular quality control and cataract formation, and finally substantially summarize the potential involvement of autophagy in the development of organelle-free zone formation.

Advanced human developmental toxicity and teratogenicity assessment using human organoid models.

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.

Comparing the accuracy of new intraocular lens power calculation formulae in short eyes after cataract surgery: a systematic review and meta-analysis.

PURPOSE: Calculating the intraocular lens (IOL) power in short eyes for cataract surgery has been a challenge. A meta-analysis was conducted to identify, among several classic and new IOL power calculation formulae, which obtains the best accuracy. METHODS: All studies aiming at comparing the accuracy of IOL power calculation formulae in short eyes were searched up in the databases of PubMed, EMBASE, Web of Science and the Cochrane library from Jan. 2011 to Mar. 2021. Primary outcomes were the percentages of eyes with a refractive prediction error in ± 0.25D, ± 0.5D and ± 1.0D. RESULTS: Totally 1,476 eyes from 14 studies were enrolled in comparison of 13 formulae (Barrett Universal II, Castrop, Haigis, Hoffer Q, Holladay1, Holladay2, Kane, Ladas Super Formula, Okulix, Olsen, Pearl-DGS, SRK/T and T2). Pearl-DGS had the highest percentage within ± 0.25D. In the ± 0.5D range, Pearl-DGS obtained the highest percentage again, and it was significantly higher than Barrett Universal II, Haigis, Hoffer Q, Holladay1, Holladay2 and Olsen (P = 0.001, P = 0.02, P = 0.0003, P = 0.01, P = 0.007, P = 0.05, respectively). In the ± 1.0D range, Okulix possessed the highest percentage, and it was significantly higher than Barrett Universal II, Castrop, Hoffer Q and Holladay2 (P = 0.0005, P = 0.03, P = 0.003, P = 0.02, respectively). CONCLUSION: The new generation formulae, based on artificial intelligence or ray-tracing principle, are more accurate than the convergence formulae. Pearl-DGS and Okulix are the two most accurate formulae in short eyes.

Functional assessment of cryopreserved clinical grade hESC-RPE cells as a qualified cell source for stem cell therapy of retinal degenerative diseases.

The biosafety and efficiency of transplanting retinal pigment epithelial (RPE) cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been evaluated in phase I and phase II clinical trials. For further large-scale application, cryopreserved RPE cells must be used; thus, it is highly important to investigate the influence of cryopreservation and thawing on the biological characteristics of hESC-RPE cells and their post-transplantation vision-restoring function. Here, via immunofluorescence, qPCR, transmission electron microscopy, transepithelial electrical resistance, and enzyme-linked immunosorbent assays (ELISAs), we showed that cryopreserved hESC-RPE cells retained the specific gene expression profile, morphology, ultrastructure, and maturity-related functions of induced RPE cells. Additionally, cryopreserved hESC-RPE cells exhibited a polarized monolayer, tight junction, and gap junction structure and an in vitro nanoparticle phagocytosis capability similar to those of induced hESC-RPE cells. However, the level of pigment epithelium-derived factor (PEDF) secretion was significantly decreased in cryopreserved hESC-RPE cells. Royal College of Surgeons rats with cryopreserved hESC-RPE cells engrafted into the subretinal space exhibited a significant decrease in the b-wave amplitude compared with rats engrafted with induced hESC-RPE cells at 4 weeks post transplantation. However, the difference disappeared at 8 weeks and 12 weeks post operation. No significant difference in the outer nuclear layer (ONL) thickness was observed between the two groups. Our data showed that even after cryopreservation and thawing, cryopreserved hESC-RPE cells are still qualified as a donor cell source for cell-based therapy of retinal degenerative diseases.

Intravitreal dexamethasone implants versus intravitreal anti-VEGF treatment in treating patients with retinal vein occlusion: a meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice.

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.

Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life.

Ethanol (EtOH) exposure during early postnatal life triggers obvious neurotoxic effects on the developing hippocampus and results in long-term effects on hippocampal neurogenesis. Resveratrol (RSV) has been demonstrated to exert potential neuroprotective effects by promoting hippocampal neurogenesis. However, the effects of RSV on the EtOH-mediated impairment of hippocampal neurogenesis remain undetermined. Thus, mice were pretreated with RSV and were later exposed to EtOH to evaluate its protective effects on EtOH-mediated toxicity during hippocampal development. The results indicated that a brief exposure of EtOH on postnatal day 7 resulted in a significant impairment in hippocampal neurogenesis and a depletion of hippocampal neural precursor cells (NPCs). This effect was attenuated by pretreatment with RSV. Furthermore, EtOH exposure resulted in a reduction in spine density on the granular neurons of the dentate gyrus (DG), and the spines exhibited a less mature morphological phenotype characterized by a higher proportion of stubby spines and a lower proportion of mushroom spines. However, RSV treatment effectively reversed these responses. We further confirmed that RSV treatment reversed the EtOH-induced down-regulation of hippocampal pERK and Hes1 protein levels, which may be related to the proliferation and maintenance of NPCs. Furthermore, EtOH exposure in the C17.2 NPCs also diminished cell proliferation and activated apoptosis, which could be reversed by pretreatment of RSV. Overall, our results suggest that RSV pretreatment protects against EtOH-induced defects in neurogenesis in postnatal mice and may thus play a critical role in preventing EtOH-mediated toxicity in the developing hippocampus.

Neuroprotective effect of memantine on the retinal ganglion cells of APPswe/PS1ΔE9 mice and its immunomodulatory mechanisms.

Besides the cognitive impairment and degeneration in the brain, vision dysfunction and retina damage are always prevalent in patients with Alzheimer's disease (AD). The uncompetitive antagonist of the N-methyl-d-aspartate receptor, memantine (MEM), has been proven to improve the cognition of patients with AD. However, limited information exists regarding the mechanism of neurodegeneration and the possible neuroprotective mechanisms of MEM on the retinas of patients with AD. In the present study, by using APPswe/PS1ΔE9 double transgenic (dtg) mice, we found that MEM rescued the loss of retinal ganglion cells (RGCs), as well as improved visual impairments, including improving the P50 component in pattern electroretinograms and the latency delay of the P2 component in flash visual evoked potentials of APPswe/PS1ΔE9 dtg mice. The activated microglia in the retinas of APPswe/PS1ΔE9 dtg mice were also inhibited by MEM. Additionally, the level of glutamine synthetase expressed by Müller cells within the RGC layer was upregulated in APPswe/PS1ΔE9 dtg mice, which was inhibited by MEM. Simultaneously, MEM also reduced the apoptosis of choline acetyl transferase-immunoreactive cholinergic amacrine cells within the RGC layer of AD mice. Moreover, the phosphorylation level of extracellular regulated protein kinases 1 and 2 was increased in APPswe/PS1ΔE9 dtg mice, which was blocked by MEM treatment. These findings suggest that MEM protects RGCs in the retinas of APPswe/PS1ΔE9 dtg mice by modulating the immune response of microglia and the adapted response of Müller cells, making MEM a potential ophthalmic treatment alternative in patients with AD.

MicroRNA-1225-5p Promotes the Development of Fibrotic Cataracts via Keap1/Nrf2 Signaling.

PURPOSE: 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. METHODS: 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-ß2 induced PCO model of human LECs and injury-induced ASC model in mice. RESULTS: 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-ß2 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. CONCLUSIONS: 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.

Carbon Monoxide Releasing Molecule-3 Alleviates Oxidative Stress and Apoptosis in Selenite-Induced Cataract in Rats via Activating Nrf2/HO-1 Pathway.

PURPOSE: This study investigated the protective effect of carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide, on selenite-induced cataract in rats and explore its possible mechanism. METHODS: Sprague-Dawley rat pups treated with sodium selenite (Na2SeO3) were chosen as the cataract model. Fifty rat pups were randomly divided into 5 groups: Control group, Na2SeO3 (3.46 mg/kg) group, low-dose CORM-3 (8 mg/kg/d) + Na2SeO3 group, high-dose CORM-3 (16 mg/kg/d) + Na2SeO3 group, and inactivated CORM-3 (iCORM-3) (8 mg/kg/d) + Na2SeO3 group. The protective effect of CORM-3 was tested by lens opacity scores, hematoxylin and eosin staining, TdT-mediated dUTP nick-end labeling assay, and enzyme-linked immunosorbent assay. Besides, quantitative real-time PCR and western blotting were used for mechanism validation. RESULTS: Na2SeO3 induced nuclear cataract rapidly and stably, and the achievement ratio of Na2SeO3 group was 100%. CORM-3 alleviated lens opacity of selenite-induced cataract and attenuated the morphological changes of the rat lens. The levels of antioxidant enzymes GSH and SOD in rat lens were also increased by CORM-3 treatment. CORM-3 significantly reduced the ratio of apoptotic lens epithelial cells, besides, CORM-3 decreased the expression of Cleaved Caspase-3 and Bax induced by selenite and increased the expression of Bcl-2 in rat lens inhibited by selenite. Moreover, Nrf-2 and HO-1 were upregulated and Keap1 was downregulated after CORM-3 treatment. While iCORM-3 did not exert the same effect as CORM-3. CONCLUSIONS: Exogenous CO released from CORM-3 alleviates oxidative stress and apoptosis in selenite-induced rat cataract via activating Nrf2/HO-1 pathway. CORM-3 may serve as a promising preventive and therapeutic strategy for cataract.

Protective effects of resveratrol on the ethanol-induced disruption of retinogenesis in pluripotent stem cell-derived organoids.

Prenatal alcohol exposure-induced fetal alcohol syndrome (FAS) can lead to serious maldevelopment in many organ systems, including the eyes. In the present study, the effects of alcohol exposure on early development of the human retina and the therapeutic effects of resveratrol on alcohol-induced neural retinal damage were observed for the first time in an in vitro retinal organoid model. We report that the number of proliferating and apoptotic cells decreased and increased, respectively, following ethanol treatment. In addition, the number of PAX6+ cells and migrating TUJ1+ cells decreased after ethanol exposure. However, pretreatment with resveratrol prevented all of these negative effects. Using RNA sequencing and immunofluorescence, we identified activation of the PI3K-AKT signalling pathway as the possible mechanism through which resveratrol protects the retina from alcohol-induced damage. These results suggest that while ethanol exposure can restrict the growth of the human retina and impede the development of specific retinal cells, pretreatment with resveratrol may be a feasible method for preventing these effects.

Generating Neural Retina from Human Pluripotent Stem Cells.

Retinopathy is one of the main causes of blindness worldwide. Investigating its pathogenesis is essential for the early diagnosis and timely treatment of retinopathy. Unfortunately, ethical barriers hinder the collection of evidence from humans. Recently, numerous studies have shown that human pluripotent stem cells (PSCs) can be differentiated into retinal organoids (ROs) using different induction protocols, which have enormous potential in retinopathy for disease modeling, drug screening, and stem cell-based therapies. This study describes an optimized induction protocol to generate neural retina (NR) that significantly reduces the probability of vesiculation and fusion, increasing the success rate of production until day 60. Based on the ability of PSCs to self-reorganize after dissociation, combined with certain complementary factors, this new method can specifically drive NR differentiation. Furthermore, the approach is uncomplicated, cost-effective, exhibits notable repeatability and efficiency, presents encouraging prospects for personalized models of retinal diseases, and supplies a plentiful cell reservoir for applications such as cell therapy, drug screening, and gene therapy testing.

Influence of hypoxia on retinal progenitor and ganglion cells in human induced pluripotent stem cell-derived retinal organoids.

AIM: To observe the effect of low oxygen concentration on the neural retina in human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs). METHODS: The hiPSC and a three-dimensional culture method were used for the experiments. Generated embryoid bodies (EBs) were randomly and equally divided into hypoxic and normoxic groups. Photographs of the EBs were taken on days 38, 45, and 52, and the corresponding volume of EBs was calculated. Simultaneously, samples were collected at these three timepoints, followed by fixation, sectioning, and immunofluorescence. RESULTS: The proportion of Ki67-positive proliferating cells increased steadily on day 38; this proliferation-promoting effect tended to increase tissue density rather than tissue volume. On days 45 and 52, the two groups had relatively similar ratios of Ki67-positive cells. Further immunofluorescence analysis showed that the ratio of SOX2-positive cells significantly increased within the neural retina on day 52 (P<0.05). In contrast, the percentage of PAX6- and CHX10-positive cells significantly decreased following hypoxia treatment at all three timepoints (P<0.01), except for CHX10 at day 45 (P>0.05). Moreover, the proportion of PAX6-/TUJ1+ cells within the neural retinas increased considerably (P<0.01, <0.05, <0.05 respectively). CONCLUSION: Low oxygen promotes stemness and proliferation of neural retinas, suggesting that hypoxic conditions can enlarge the retinal progenitor cell pool in hiPSC-derived ROs.

Rapid bilateral visual loss as the initial clinical manifestation in idiopathic hypertrophic cranial pachymeningitis.

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.

Risk of anxiety and depression in patients with uveitis: a Meta-analysis.

AIM: To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Meta-analysis. METHODS: Three electronic database (PubMed, Embase, and Cochrane Library databases) were searched for studies recording data about uveitis and anxiety as well as depression simultaneously up to January 2021. The incidence rate and standard mean difference (SMD) with a 95% confidence interval (95%CI) were calculated to analyse the association using random-effects models based on heterogeneity tests. RESULTS: In total, 12 observational studies containing 874 patients with uveitis were included. The results showed that there was a significant association between uveitis and anxiety (SMD=0.97, 95%CI: 0.39 to 1.54, P=0.0009) and depression (SMD=0.79, 95%CI: 0.51 to 1.07, P<0.00001). The overall morbidities of anxiety and depression in patients with uveitis were 39% and 17%, respectively. With subgroup analysis, the heterogeneity actually came from different kinds of uveitis. Specifically, the incidence rates of both anxiety and depression were relatively low in patients with anterior uveitis (33% and 15%), moderate in patients with infectious uveitis (46% and 22%), and high in patients with unspecified uveitis (59% and 35%). CONCLUSION: It is preliminarily indicated that patients with uveitis may have a high risk of anxiety and depression. Ophthalmologists and psychologists should pay more attention to the psychological state when dealing with patients with uveitis. Further high-quality studies with detailed direct data are needed to draw more precise conclusions.

A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.

The lens is a relatively special and simple organ. It has become an ideal model to study the common developmental characteristics among different organic systems. Lens development is a complex process influenced by numerous factors, including signals from the intracellular and extracellular environment. Reactive oxygen species (ROS) are a group of highly reactive and oxygen-containing molecules that can cause endoplasmic reticulum stress in lens cells. As an adaptive response to ER stress, lens cells initiate the unfolded protein response (UPR) to maintain normal protein synthesis by selectively increasing/decreasing protein synthesis and increasing the degradation of misfolded proteins. Generally, the UPR signaling pathways have been well characterized in the context of many pathological conditions. However, recent studies have also confirmed that all three UPR signaling pathways participate in a variety of developmental processes, including those of the lens. In this review, we first briefly summarize the three stages of lens development and present the basic profiles of ROS and the UPR. We then discuss the interconnections between lens development and these two mechanisms. Additionally, the potential adoption of human pluripotent stem-cell-based lentoids in lens development research is proposed to provide a novel perspective on future developmental studies.

Differentially expressed gene profiles and associated ceRNA network in ATG7-Deficient lens epithelial cells under oxidative stress.

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 via the packages "clusterProfiler" and "enrichplot". We found that after the knockout of ATG7, differentially expressed genes were more associated with hemopoiesis, vasculature development, axonogenesis, and hypoxia regulation. When stimulated with H2O2, 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 H2O2 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.

Two-dimensional ultrathin Ti3C2 MXene nanosheets coated intraocular lens for synergistic photothermal and NIR-controllable rapamycin releasing therapy against posterior capsule opacification.

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@Ti3C2-IOL), prepared from two-dimensional ultrathin Ti3C2 MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti3C2 was prepared via electrostatic self-assembly of Ti3C2 and Rapa, with a loading capacity of Rapa at 92%. Ti3C2 was used as a drug delivery reservoir of Rapa. Rapa@Ti3C2-IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti3C2-IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti3C2 coating effectively eliminated the LECs around Rapa@Ti3C2-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@Ti3C2-IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti3C2-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 Ti3C2 MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties.

Shaping the Microglia in Retinal Degenerative Diseases Using Stem Cell Therapy: Practice and Prospects.

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.