Taurine: a promising nutraceutic in the prevention of retinal degeneration

Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal tract.To investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal tract.We first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal tract.An antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time points.To improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing axons.Using this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after stroke.In addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over time.Meanwhile,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian degeneration.Moreover,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal tract.In conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration:potential therapeutic implications

Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.

Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration

The retinal pigment epithelium(RPE)is fundamental to sustaining retinal homeostasis.RPE abnormality leads to visual defects and blindness,including age-related macular degeneration(AMD).Although breakthroughs have been made in the treatment of neovascular AMD,effective intervention for atrophic AMD is largely absent.The adequate knowledge of RPE pathology is hindered by a lack of the patients'RPE datasets,especially at the single-cell resolution.In the current study,we delved into a large-scale single-cell resource of AMD donors,in which RPE cells were occupied in a substantial proportion.Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD.Both in vivo and in vitro models revealed that carboxypeptidase X,M14 family member 2(CPXM2),was specifically expressed in the RPE cells of atrophic AMD,which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells.Additionally,silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model.Thus,our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.

Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration:An observational study

BACKGROUND Anti-vascular endothelial growth factor(anti-VEGF)therapy is critical for managing neovascular age-related macular degeneration(nAMD),but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.AIM To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.METHODS In this study,65 eyes of exudative AMD patients after anti-VEGF treatment for≥1 mo were observed using optical coherence tomography angiography.Patients were classified into non-responders(n=22)and responders(n=43).Logistic regression was used to determine independent risk factors for treatment response.A predictive model was created using the Akaike Information Criterion,and its performance was assessed with the area under the receiver operating characteristic curve,calibration curves,and decision curve analysis(DCA)with 500 bootstrap re-samples.RESULTS Multivariable logistic regression analysis identified the number of junction voxels[odds ratio=0.997,95%confidence interval(CI):0.993-0.999,P=0.010]as an independent predictor of positive anti-VEGF treatment outcomes.The predictive model incorporating the fractal dimension,number of junction voxels,and longest shortest path,achieved an area under the curve of 0.753(95%CI:0.622-0.873).Calibration curves confirmed a high agreement between predicted and actual outcomes,and DCA validated the model's clinical utility.CONCLUSION The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy,enhancing personalized treatment planning.

Investigating the causal link between gut microbiota and dry age-related macular degeneration:a bidirectional Mendelian randomization study

AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study(GWAS)were used.Inverse variance weighted(IVW)analysis and sensitivity analysis were performed on the FinnGen project,which included 5095 cases and 222590 controls.RESULTS:The IVW analysis showed substantial genusand family-level relationships between GM taxa and dAMD risk.Specifically,the family Peptococcaceae(P=0.03),genus Bilophila(P=3.91×10^(-3)),genus Faecalibacterium(P=6.55×10^(-3)),and genus Roseburia(P=0.04)were linked to a higher risk of developing dAMD,while the genus Candidatus Soleaferrea(P=7.75×10^(-4)),genus Desulfovibrio(P=0.04)and genus Eubacterium ventriosum group(P=0.04)exhibited a protective effect against dAMD.No significant causal relationships were observed at higher taxonomic levels.Additionally,in the reverse IVW analysis,no meaningful causal effects of the 7 GM taxa.CONCLUSION:These findings give support for the gutretina axis participation in dAMD and shed light on putative underlying processes.Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

Novel insights into the mechanism of reactive oxygen species-mediated neurodegeneration

Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,but rather it appears that a self-destructive process is in action.Oxidative stress is a well-known inducer of neurodegenerative pathways:neuronal cell death and neurite degeneration.Although oxidative stress exerts cytotoxic effects leading to neuronal loss,the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown.We previously reported that reactive oxygen species generated by NADPH oxidases induce activation of the E3 ubiquitin ligase ZNRF1 in neurons,which promotes neurite degeneration.In this process,the phosphorylation of an NADPH oxidase subunit p47-phox at the 345serine residue serves as an important checkpoint to initiate the ZNRF1-dependent neurite degeneration.Evidence provides new insights into the mechanism of reactive oxygen species-mediated neurodegeneration.In this review,we focus specifically on reactive oxygen species-induced neurite degeneration by highlighting a phosphorylation-dependent regulation of the molecular interaction between ZNRF1 and the NADPH oxidase complex.

Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain

Spine degeneration is an aging-related disease,but its molecular mechanisms remain unknown,although elevatedβ-catenin signaling has been reported to be involved in intervertebral disc degeneration.Here,we determined the role ofβ-catenin signaling in spinal degeneration and in the homeostasis of the functional spinal unit(FSU),which includes the intervertebral disc,vertebra and facet joint and is the smallest physiological motion unit of the spine.We showed that pain sensitivity in patients with spinal degeneration is highly correlated withβ-catenin protein levels.We then generated a mouse model of spinal degeneration by transgenic expression of constitutively activeβ-catenin in Col2^(+) cells.We found thatβ-catenin-TCF7 activated the transcription of CCL2,a known critical factor in osteoarthritic pain.Using a lumbar spine instability model,we showed that aβ-catenin inhibitor relieved low back pain.Our study indicates thatβ-catenin plays a critical role in maintaining spine tissue homeostasis,its abnormal upregulation leads to severe spinal degeneration,and its targeting could be an avenue to treat this condition.

cGMP signaling:a potential therapeutic target for neurodegeneration in glaucoma?

Neurodegeneration of the central nervous system(CNS)underscores many of humanity’s most debilitating diseases,including Alzheimer’s disease,Parkinson’s disease,and multiple sclerosis.Recently,the nitric oxide-guanylate cyclase-cyclic guanosine monophosphate(NOGC-cGMP)signaling pathway has gained traction as a neuroprotective pathway in the CNS.As an extension of the CNS,the retina is also susceptible to neurodegeneration with age.The most prevalent optic neuropathy is glaucoma,the world’s leading cause of irreversible blindness,predicted to affect more than 112 million people worldwide by 2040(Calkins,2021).In glaucoma,vision loss occurs due to the progressive degeneration of retinal ganglion cells(RGCs),the output neurons of the retina,along with their axons which form the optic nerve(Wareham et al.,2022).Degeneration of RGCs leads to a characteristic pattern of scotopic visual field deficiencies that spread from one retinotopic sector to the next(Elze et al.,2015).Visual deficits are linked to increasing age and the sensitivity of RGCs to intraocular pressure(Calkins,2021).

Oxidative stress in retinal pigment epithelium degeneration:from pathogenesis to therapeutic targets in dry age-related macular degeneration

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration;however, effective treatment is not yet available for geographical atrophy in dry agerelated macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human agerelated macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Extracellular vesicles as a potential therapeutic for age-related macular degeneration

Age-related macular degeneration is a major global cause of central visual impairment and seve re vision loss.With an aging population,the already immense economic burden of costly anti-vascular endothelial growth fa ctor treatment is likely to increase.In addition,current conventional treatment is only available for the late neovascular stage of age-related macular degeneration,and injections can come with potentially devastating complications,introducing the need for more economical and ris kfree treatment.In recent years,exosomes,which are nano-sized extracellular vesicles of an endocytic origin,have shown immense potential as diagnostic biomarkers and in the therapeutic application,as they are bestowed with characte ristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells.Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases;however,exosomes as a potential therapy for seve ral retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically.This article will focus on the limited literature availa ble on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures,as well as briefly identify future research directions.Current literature on exosome therapy using agerelated macular degeneration rodent models includes laser retinal injury,N-methyl-N-nitrosourea,and royal college of surgeon models,which mimic inflammatory and degenerative aspects of agerelated macular degeneration.These have shown promising results in preserving retinal function and morphology,as well as protecting photoreceptors from apoptosis.Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cyto kines,mRNAs,and proteins involved in photo receptor degeneration pathways to exert a therapeutic effect.Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.

Neural and Müller glial adaptation of the retina to photoreceptor degeneration

The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors,which leads to progressive loss of vision.The inner retina,including second-and third-order retinal neurons,also shows aberrant structural changes at all stages of degeneration.Müller glia,the major glial cells maintain retinal homeostasis,activating and rearranging immediately in response to photoreceptor stress.These phenomena are collectively known as retinal remodeling and are anatomically well described,but their impact on visual function is less well characterized.Retinal remodeling has traditionally been considered a detrimental chain of events that decreases visual function.However,emerging evidence from functional assays suggests that remodeling could also be a part of a survival mechanism wherein the inner retina responds plastically to outer retinal degeneration.The visual system’s first synapses between the photoreceptors and bipolar cells undergo rewiring and functionally compensate to maintain normal signal output to the brain.Distinct classes of retinal ganglion cells remain even after the massive loss of photoreceptors.Müller glia possess the regenerative potential for retinal recovery and possibly exert adaptive transcriptional changes in response to neuronal loss.These types of homeostatic changes could potentially explain the well-maintained visual function observed in patients with inherited retinal degenerative diseases who display prominent anatomic retinal pathology.This review will focus on our current understanding of retinal neuronal and Müller glial adaptation for the potential preservation of retinal activity during photoreceptor degeneration.Targeting retinal self-compensatory responses could help generate universal strategies to delay sensory disease progression.

Retinal pigment epithelium–Bruch’s membrane volume in grading of age-related macular degeneration

AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)grading.METHODS:Digital color fundus photographs(CFPs)and spectral domain OCT images were acquired from 96 elderly subjects.CFPs were graded according to Age-Related Eye Disease Study(AREDS)classification.OCT image segmentation and RBV data calculation were done with OrionTM software.Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.RESULTS:RBV correlated with AMD grading(rs=0.338,P=0.001),the correlation was slightly stronger in early AMD(n=52;rs=0.432,P=0.001).RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs(1.05±0.20 vs 0.96±0.13 mm3,P=0.023).In multivariate analysis higher RBVs were associated significantly with higher total drusen(β=0.388,P=0.027)and pigmentation areas(β=0.319,P=0.020)in fundus photographs,whereas depigmentation area(β=-0.295,P=0.015)associated with lower RBV.CONCLUSION:RBV correlate with AMD grading status,with a stronger association in patients with moderate,non-late AMD grades.This effect is driven mostly by lesions with drusen or pigmentation.Lesions with depigmentation tend to have lower values.RBV is more comprehensive measurement of the key area of AMD pathogenesis,compared to sole drusen volume analysis.RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting,but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet agerelated macular degeneration

AIM:To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration(AMD).METHODS:Fifty naïve and previously untreated patients suffering from wet AMD,were randomly assigned in two subgroups of 25 patients each.All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept(IAIs)followed by injections“according to need”,while in one group the patients also received daily two tablets of resveratrol oral supplement.Prior to treatment initiation,a complete ophthalmological examination,including best corrected visual acuity(BCVA)and contrast sensitivity evaluation,optical coherence tomography(OCT)scans,fundus autofluorescence(FAF),fluorescein angiography,indocyanine green angiography,and OCT angiography(OCTA),was performed to every participant,while all of them completed the Hospital Anxiety and Depression Scale(HADS)questionnaire,in order to assess their quality of life(QoL)status.The patients were assessed monthly for 1y with FAF,and OCT or OCTA;the main endpoints were the number IAIs,the changes in BCVA,in contrast sensitivity,and in patients’QoL status.RESULTS:No significant differences were present between the groups regarding the baseline demographic and clinical data.Over the 12-month period,a similar number of IAIs was applied in both groups(4.52±1.00 vs 4.28±0.90,P=0.38),while the rest of the clinical data also did not differ significantly after the completion of the study period.However,for HADS Depression(11.88±2.51 vs 8.28±1.54,P<0.001)and HADS Anxiety(11.92±2.52 vs 7.76±1.51,P<0.001)questionnaires values,the score was significantly better in patients who received resveratrol supplements.Moreover,a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity(0.17±0.19 vs 0.35±0.24,P=0.005),HADS Depression(0.08±1.38 vs-3.88±1.48,P<0.001),and HADS Anxiety(0.36±1.98 vs-5.12±2.70,P<0.001)scores,in favour of the patients treated with resveratrol supplements.CONCLUSION:The resveratrol oral supplement is a complementary treatment in cases of wet AMD,highlighting its effectiveness in improving patients’QoL status.

How to enhance the ability of mesenchymal stem cells to alleviate intervertebral disc degeneration

Intervertebral disc(ID)degeneration(IDD)is one of the main causes of chronic low back pain,and degenerative lesions are usually caused by an imbalance between catabolic and anabolic processes in the ID.The environment in which the ID is located is harsh,with almost no vascular distribution within the disc,and the nutrient supply relies mainly on the diffusion of oxygen and nutrients from the blood vessels located under the endplate.The stability of its internal environment also plays an important role in preventing IDD.The main feature of disc degeneration is a decrease in the number of cells.Mesenchymal stem cells have been used in the treatment of disc lesions due to their ability to differentiate into nucleus pulposus cells in a nonspecific anti-inflammatory manner.The main purpose is to promote their regeneration.The current aim of stem cell therapy is to replace the aged and metamorphosed cells in the ID and to increase the content of the extracellular matrix.The treatment of disc degeneration with stem cells has achieved good efficacy,and the current challenge is how to improve this efficacy.Here,we reviewed current treatments for disc degeneration and summarize studies on stem cell vesicles,enhancement of therapeutic effects when stem cells are mixed with related substances,and improvements in the efficacy of stem cell therapy by adjuvants under adverse conditions.We reviewed the new approaches and ideas for stem cell treatment of disc degeneration in order to contribute to the development of new therapeutic approaches to meet current challenges.

Lumbar instability remodels cartilage endplate to induce intervertebral disc degeneration by recruiting osteoclasts via Hippo-CCL3 signaling

Degenerated endplate appears with cheese-like morphology and sensory innervation,contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However,the origin and development mechanism of the cheese-like morphology remain unclear.Here in this study,we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change.

Using choroidal thickness to detect myopic macular degeneration

AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.