Investigative ophthalmology & visual science最新文献

{"title":"Retinal and Choriocapillaris Thickness Changes in Spontaneously Diabetic Macaques.","authors":"Lingli Zhou, Shuxin Fan, Haining Lu, Wenqing Zhang, Kaoru Ri, Zhenhua Xu, Xiangrong Kong, Amir H Kashani, Xialin Liu, Charles Eberhart, Wei Yi, Elia J Duh","doi":"10.1167/iovs.66.2.11","DOIUrl":"10.1167/iovs.66.2.11","url":null,"abstract":"<p><strong>Purpose: </strong>Beyond the clinically apparent damage to the retinal vasculature, diabetes affects the neuroretina and choroid. Nonhuman primates (NHPs) serve as valuable models for human retinal diseases, including diabetic retinopathy. This study aimed to investigate changes in the thickness of the retina, RPE, and choriocapillaris in spontaneously diabetic cynomolgus macaques.</p><p><strong>Methods: </strong>Optical coherence tomography (OCT) images were obtained from 25 diabetic macaques and 26 age-matched nondiabetic macaques. The thickness of individual retinal layers in the macula, along with RPE and choriocapillaris, was measured manually. Choriocapillaris thickness was assessed in postmortem human globes from diabetic and nondiabetic individuals.</p><p><strong>Results: </strong>Diabetes predominantly affected the inner retina more than the outer retina in macaques. Notably, the nasal retina showed greater thinning compared to the temporal retina. A slight but significant thickening of the inner nuclear layer was observed. No changes were detected in the thickness of RPE/Bruch's membrane complex via OCT. However, a significant increase in choriocapillaris thickness was noted in the diabetic macaques. Postmortem human specimens from patients with nonproliferative diabetic retinopathy (NPDR) also demonstrated thickening of choriocapillaris/Bruch's membrane.</p><p><strong>Conclusions: </strong>Consistent with humans, early diabetes in cynomolgus macaques results in notable alterations in retinal thickness, particularly affecting the nasal inner retina. The observed increase in choriocapillaris thickness in both diabetic macaques and human patients with NPDR likely indicates pathologic changes and remodeling due to diabetes. Cynomolgus macaque presents a valuable NHP model for studying diabetic retinopathy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"11"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 Promotes Lysosome-Dependent Cell Death Induced Via Dry Eye by Disrupting Lysosomal Homeostasis.","authors":"Xiaojuan Hu, Jiayao Feng, Chengjie Pan, Zhenzhen Sun, Jiechen Liu, Shuang Xie, Decheng Xiao, Xiaoyin Ma, Qinxiang Zheng, Wei Chen","doi":"10.1167/iovs.66.2.5","DOIUrl":"10.1167/iovs.66.2.5","url":null,"abstract":"<p><strong>Purpose: </strong>Hypertonic stress can induce apoptosis, inflammation, and dry eye disease (DED) through the upregulation of HMGB1 expression. However, its role in mediating and maintaining lysosomal homeostasis and suppressing DED development in living and in vitro models is unclear.</p><p><strong>Methods: </strong>Immunofluorescence, nucleoplasmic separation, and electron microscopic analysis were used to compare the effects of hypertonic stress on lysosomal function, nuclear HGMB1 expression, and lysosomal localization in three different dry eye models. The live model was established by the subcutaneous injection of scopolamine (SCOP) into C57BL/6J female mice, and the in vitro model used human corneal epithelial cell (HCEC) cultures that were maintained at a hyperosmotic level of 450 milliosmolar (mOsm). RNAi technology was used to knockdown HMGB1 expression levels, altering hyperosmotic stress-induced changes in survival and autophagy of corneal epithelial cells in vitro. Lysosomal protease inhibitors were applied to suppress the increase of corneal tissue inflammation in the dry eye mouse model.</p><p><strong>Results: </strong>This hypertrophic stress upregulated karyoplasmic HMGB1 expression in HCECs. This change disrupted lysosomal structural and functional integrity, which facilitated the release of HMGB1 into the cytoplasm. SiRNAs downregulated HMGB1 expression levels and reversed increases in HMGB1 transfer from the nucleus to the cytoplasm and lysosomal alkalinizing function. These changes promoted increases in cathepsin leakage from lysosomes and increased mouse corneal epithelial apoptosis, whereas autophagy decreased. In a mouse model, administration of a cathepsin inhibitor reduced both ocular inflammation and other aspects of dry eye symptomology.</p><p><strong>Conclusions: </strong>Hyperosmotic-induced HMGB1 upregulation and increased HMGB1 transfer into the cytoplasm from the nucleus underlie the loss of lysosomal membrane integrity, which increases both cathepsin release and corneal epithelial apoptosis. HMGB1 downregulation instead ameliorated these pathogenic responses.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of HSV Genomic Signatures Among Acanthamoeba Hosts and Contaminated Lens Cases: A Molecular and Clinical Study.","authors":"Juan-Carlos Navia, Alexander Alfonso, Darlene Miller, Jorge Maestre-Mesa, Heather Durkee, Paula A Sepulveda-Beltran, Felipe Echeverri-Tribin, Salomon Merikansky, Jaime D Martinez, Harry W Flynn, Eduardo C Alfonso, Jean-Marie Parel, Guillermo Amescua","doi":"10.1167/iovs.66.2.4","DOIUrl":"10.1167/iovs.66.2.4","url":null,"abstract":"<p><strong>Purpose: </strong>To document the presence of herpes simplex virus (HSV) genomic signatures among Acanthamoeba hosts recovered from patients with Acanthamoeba keratitis (AK) and in contaminated lens cases.</p><p><strong>Methods: </strong>We used a combination of PCR sequencing and shotgun metagenomics to detect and confirm the presence of HSV genomic signatures in Acanthamoeba hosts and lens cases. Clinical outcomes were correlated with the prevalence of host HSV signatures.</p><p><strong>Results: </strong>HSV genomic signatures were detected in 26% (n = 6) of Acanthamoeba hosts recovered from patients with culture confirmed AK. HSV-1 and HSV-2 or both were identified in 33%, 50%, and 17% of isolates, respectively. Fifty-two percent of patients (12/23) were misdiagnosed initially as presenting with HSV keratitis. Patients with HSV-positive Acanthamoeba isolates had a mean best-corrected visual acuity of 1.43 LogMAR at diagnosis and 0.53 LogMAR at follow-up, compared with 1.85 and 0.92 LogMAR, respectively, in HSV-negative cases. Contact lens use was identified as a risk factor in 83% of 18 patients. We detected 46,597 viral signatures in 5 of 14 contaminated lens cases (35.7%). Distribution included 33% bacteriophages, 8.2% giant viruses, 4.1% nonhuman Herpesviridae, and 0.39% human Herpesviridae. Among the 184 human Herpesviridae genomic signatures, HSV types 1 or 2 or both were documented in 5.7%, VZV in 39.7%, HHV7 in 38.6%, HHV6 in 15.0%, and Epstein-Barr virus in 0.5%.</p><p><strong>Conclusions: </strong>This study is the first to identify HSV-positive genomic signatures in clinical AK isolates and/or contact lens cases. Taken together, the high prevalence of HSV genomic signatures in both amebic hosts and lens cases, might signal an unrecognized Acanthamoeba-HSV association and the need for reassessing current management.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Refraction and Axial Growth Rate After Multifocal or Monofocal Intraocular Lens Implantation in Chinese Pediatric Cataract Patients.","authors":"Qiuxuan Du, Ying Zhang, Yusen Huang","doi":"10.1167/iovs.66.2.33","DOIUrl":"10.1167/iovs.66.2.33","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to compare relative peripheral refraction (RPR) and axial growth in Chinese pediatric patients with cataract who underwent multifocal or monofocal intraocular lens (IOL) implantation.</p><p><strong>Methods: </strong>Pediatric patients with cataract aged 3 to 6 years who underwent IOL implantation from 2020 to 2021 were enrolled in this study. The patients received multifocal or monofocal IOL implantations with optic capture in Berger's space. The axial length (AL) was measured with a Zeiss IOL Master 700, and autorefraction at the horizontal retina within 30 degrees eccentricities was recorded with a Grand Seiko WAM-5500 autorefractor. The RPR was calculated by subtracting the central refraction from the peripheral refraction. The axial growth rate was calculated as the change in the AL divided by the number of follow-up years.</p><p><strong>Results: </strong>Twenty-six children (38 eyes) implanted with multifocal IOLs and 19 children (30 eyes) implanted with monofocal IOLs completed the study. No significant differences were observed in preoperative characteristics between the two groups (P > 0.05). The generalized estimating equation (GEE) model revealed that the axial growth rate was significantly associated with the IOL type (P = 0.049) after adjusting for surgical age and follow-up intervals, with multifocal IOL eyes showing lower annual growth rate than monofocal IOL eyes. Additionally, compared with monofocal IOL eyes, multifocal IOL eyes exhibited greater peripheral myopic defocus at 20 degrees and 30 degrees on the temporal retina (P < 0.001 and P = 0.005, respectively). The GEE model also revealed a positive correlation between the annual axial growth rate and the 20 degrees temporal retina RPR (P = 0.018).</p><p><strong>Conclusions: </strong>Chinese pediatric patients with cataract who underwent multifocal IOL implantation exhibited less axial growth, potentially caused by greater peripheral myopic defocus.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"33"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Runx1 in Pathological Retinal Angiogenesis: A Potential Therapeutic Approach.","authors":"Xiaoyan Ding, Xiaodi Zhou, Xinyu Liu, Yanting Lai, Wenjia Yan, Yizhe Cheng, Aohan Hou, Limei Chen, Limei Sun","doi":"10.1167/iovs.66.2.40","DOIUrl":"10.1167/iovs.66.2.40","url":null,"abstract":"<p><strong>Purpose: </strong>Neovascular eye diseases, such as proliferative diabetic retinopathy (PDR), wet age-related macular degeneration (wAMD) and retinopathy of prematurity (ROP), are major causes of vision loss and blindness worldwide. Our transcription factor motif enrichment analysis highlighted RUNX1 as a key regulator in the hypoxic response. The purpose of this study was to characterize how loss of Runx1 affects physiological and pathological retinal vasculature formation.</p><p><strong>Methods: </strong>RNA-seq analysis and Transcription factor motif enrichment analysis were conducted in hypoxic and normoxic HUVECs. Conditional deletion of Runx1 in endothelial cells In mice was achieved using recombinase driver Cdh5-CreERT2. Vascular coverage, density, vessel progression, branchpoints, and sprout numbers was measured in retina of Runx1iECKO mice. The expression patterns, functions, and potential therapeutic value of RUNX1 were further explored with clinical samples, as well as in vivo and in vitro experiments. Bioinformatics and high-throughput sequencing were performed to identify potential target genes of Runx1. RT-qPCR and Western blot analyses were carried out to detect the changes of PI3-kinase/AKT/mTOR pathway.</p><p><strong>Results: </strong>Loss of Runx1 in mice resulted in a reduction of the vascular coverage, density, vessel progression, branchpoints, and sprouts numbers of the retinal vascular network during its development. Notably, mature blood vessels remained unaffected by Runx1 inhibition. Upregulation of RUNX1 was observed in patients with PDR and ROP. RUNX1 Inhibition reduced endothelial cell proliferation, migration and tubule formation, leading to decreased pathological neovascularization, which is shown in oxygen-induced retinopathy. Mechanistically, in vitro experiments demonstrated that RUNX1 regulates EC angiogenesis through the PI3K/AKT/mTOR signaling pathway.</p><p><strong>Conclusions: </strong>Runx1 is essential for physiological retinal vascularization. RUNX1 Inhibition may effectively decrease pathological neovascularization. Our findings suggest that targeting RUNX1 could be a promising therapeutic strategy for retinal neovascular disorders, preserving the integrity of mature blood vessels while selectively inhibiting neovascularization.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"40"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aurora A Kinase Inhibition Is Synthetic Lethal With the Activation of MYCN in Retinoblastoma.","authors":"Qili Liao, Jie Yang, Hanhan Shi, Reyizha Mengjiang, Yongyun Li, Qianqian Zhang, Xuyang Wen, Shengfang Ge, Peiwei Chai, Xianqun Fan, Renbing Jia, Jiayan Fan","doi":"10.1167/iovs.66.2.20","DOIUrl":"10.1167/iovs.66.2.20","url":null,"abstract":"<p><strong>Purpose: </strong>RB1 inactivation and MYCN activation have been documented as common oncogenic alterations in retinoblastoma (RB). Direct targeting of RB1 and MYCN has not yet been proven to be feasible. The current treatment options for RB mainly consist of conventional chemotherapy, which inevitably poses health-threatening side effects. Here, we aimed to screen an in-house compound library to identify potential drugs for the treatment of human RB.</p><p><strong>Methods: </strong>Aurora A kinase (AURKA) inhibitors were identified by differential viability screening with a tool compound library, and the pharmacological safety and efficacy of candidate drugs were further validated in zebrafish and RB patient-derived xenograft (PDX) models in vivo. Further CUT & Tag assay, ChIP-qPCR and RNA seq performances showed that MYCN binds to the AURKA promoter and upregulates its transcription, suggesting that AURKA inhibition induces synthetic lethality in RB.</p><p><strong>Results: </strong>In this study, we revealed that AURKA inhibitors exhibited high therapeutic efficacy against RB both in vitro and in vivo. Mechanistically, we found that MYCN could bind to the AURKA promoter region to regulate its transcription, thereby promoting AURKA expression and consequently driving RB progression. Interestingly, AURKA inhibition exhibited synthetic lethality with RB1-deficient and MYCN-amplification in RB cells.</p><p><strong>Conclusions: </strong>Collectively, these findings demonstrate that AURKA is crucial for RB progression and further expanded the current understanding of synthetic lethal therapeutic strategies. Our study indicates that AURKA inhibitors may represent a new therapeutic strategy for selectively targeting patients with RB with RB1-deficient and MYCN-amplification to improve the prognosis of aggressive types of patients with RB.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"20"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Responses to Short- and Longer-Term Predominant ON or OFF Stimulation in Emmetropes and Myopes.","authors":"Sandra Wagner, Annemarie Settele, Torsten Strasser","doi":"10.1167/iovs.66.2.66","DOIUrl":"10.1167/iovs.66.2.66","url":null,"abstract":"<p><strong>Purpose: </strong>The link between nearwork and myopia is controversially discussed. Features of the viewing target may stimulate eye growth, for example, black-on-white text was found to stimulate retinal OFF pathways and promote choroidal thinning, whereas inverted text led to ON pathway stimulation and thicker choroids. We used electroretinograms (ERGs) to compare retinal activity for both stimuli in the parafovea in emmetropes and myopes and studied the effects of adaptation.</p><p><strong>Methods: </strong>ERGs were recorded in 42 subjects (18-30 years) during 200 ms-flashes on a CRT monitor, superimposed with an annulus or circles filled with gray or inverted or standard text. Ganzfeld ERGs (500 ms) were taken before and after 30 minutes of reading standard or inverted text at 25 cm to determine adaptation effects. The ON- (b-wave) and OFF-responses (d-wave) were analyzed using linear mixed effects models and pointwise t-testing.</p><p><strong>Results: </strong>(1) Stimulus size affected retinal ON-responses of both groups (p < 0.001), with larger responses to a 6 to 12 degrees annulus than to a 12-degree circle. (2) Myopes displayed larger ON-responses to inverted text contrast than emmetropes within 6 to 12 degrees. (3) After adaptation to text, ON-responses were reduced (p = 0.010) irrespective of refraction and contrast. (4) Emmetropes showed reduced ON- and OFF-responses to inverted text contrast. (5) Only emmetropes had reduced ON- and larger OFF-responses after adapting to standard text.</p><p><strong>Conclusions: </strong>Myopes had largest ON-responses with inverted contrast in the perifovea. Emmetropes displayed larger adaptive changes after ON/OFF stimulation. In both groups, inverted contrast still reduced ON-responses, suggesting that efficient activation of retinal ON channels to inhibit myopia might require additional OFF channel suppression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"66"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Signature of Serum Modified Nucleosides in Uveitis.","authors":"Haoze Zhou, Yiqiu Hu, Guangming Qin, Jinfeng Kong, Xiujuan Hong, Cheng Guo, Jian Zou, Lei Feng","doi":"10.1167/iovs.66.2.68","DOIUrl":"10.1167/iovs.66.2.68","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate the metabolism of serum-modified nucleosides in uveitis by using liquid chromatography-tandem mass spectrometry (LC-MS) and to develop potential diagnostic biomarkers for uveitis.</p><p><strong>Methods: </strong>Forty-two patients with different subtypes of uveitis (idiopathic uveitis, Vogt-Koyanagi-Harada [VKH] disease, and ankylosing spondylitis [AS]) and 32 healthy controls were recruited in this retrospective case-control study. The concentrations of 23 modified nucleosides in patient serum were quantified by LC-MS. The data was statistically analyzed with SPSS and GraphPad Prism.</p><p><strong>Results: </strong>The data revealed that 13 out of 23 modified nucleosides (m6A, m1A, m6Am, Cm, ac4C, Gm, m1G, m2G, m2,2G, Um, m3U, m5U, and m5Um) effectively showed quantifiable chromatographic peaks. The statistical results indicated that there were extremely significant differences for m2G, Gm, Cm, and m1G between healthy controls and uveitis patients. The differences for Gm, m6A,and m5U were able to further assort idiopathic uveitis and uveitis with systemic inflammation including VKH and AS. Interestingly, each specific subtype of uveitis is characterized by its signature combination of serum-modified nucleotides comparing with healthy controls.</p><p><strong>Conclusions: </strong>This study revealed that the metabolism of serum-modified nucleosides in uveitis patients display significant differences from healthy controls. The signature combination of serum modified nucleotides for each subtype of uveitis may be applied for the potential diagnosis of uveitis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"68"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrastructural Aspects of Corneal Functional Recovery in Rats Following Intrastromal Keratocyte Injection.","authors":"Qian Ma, Andri K Riau, Robert D Young, James S Bell, Olga Shebanova, Nicholas J Terrill, Gary H F Yam, Evelina Han, Keith M Meek, Jodhbir S Mehta, Craig Boote","doi":"10.1167/iovs.66.2.45","DOIUrl":"10.1167/iovs.66.2.45","url":null,"abstract":"<p><strong>Purpose: </strong>Donor tissue shortfalls and postsurgical complications are driving novel corneal tissue regeneration approaches. Corneal stromal keratocytes (CSKs) have shown promise in promoting corneal repair and restoring transparency. We investigated the impact of intrastromal CSK injection on corneal ultrastructure and proteoglycan (PG) distribution in a rat injury model.</p><p><strong>Methods: </strong>Rats were divided into four groups: normal (n = 12), injured (irregular phototherapeutic keratectomy centrally; n = 6), CSK (injured + human CSK intrastromal injection; n = 6), and PBS (injured + PBS injection; n = 6). Three weeks after treatment, corneas were examined by slit-lamp and optical coherence tomography. Corneal ultrastructure was analysed via small-angle x-ray scattering (collagen fibril diameter, interfibrillar spacing and matrix order), transmission electron microscopy with cuprolinic blue before and after chondroitinase digestion (CS/DS and KS PGs), and immunofluorescence staining (lumican and decorin).</p><p><strong>Results: </strong>Irregular phototherapeutic keratectomy caused corneal opacity and significantly disrupted stromal ultrastructure, characterized by increased haze density (P < 0.0001), change in central corneal thickness (P = 0.0005), and interfibrillar spacing (P < 0.0001), along with decreased fibril diameter (P < 0.0001), matrix order (P < 0.0001), CS/DS (P < 0.0001) and KS (P < 0.0001) PGs, lumican, and decorin. CSK injection recovered corneal clarity and native stromal ultrastructure, with haze density (P = 0.8086), change in central corneal thickness (P = 0.9503), fibril diameter (P = 0.1139), interfibrillar spacing (P = 0.5879), matrix order (P = 0.9999), CS/DS (P = 0.9969) and KS (P = 0.2877) PGs, lumican, and decorin returning to normal. In contrast, the PBS group exhibited similar corneal injury responses to the injured group.</p><p><strong>Conclusions: </strong>CSK injection resolved early stage corneal scarring by restoring stromal collagen arrangement and PG distribution, further endorsing its potential for treating corneal opacities.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"45"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11838119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depth and Strain-Dependent Structural Responses of Mouse Lens Fiber Cells During Whole Lens Shape Changes.","authors":"Sepideh Cheheltani, Mahbubul H Shihan, Justin Parreno, Sondip K Biswas, Woo-Kuen Lo, Velia M Fowler","doi":"10.1167/iovs.66.2.53","DOIUrl":"10.1167/iovs.66.2.53","url":null,"abstract":"<p><strong>Purpose: </strong>To study the relationship between whole lens shape changes and fiber cell responses to externally applied loads.</p><p><strong>Methods: </strong>Freshly dissected mouse lenses were compressed by applying glass coverslips to the lens anterior, followed by fixation to preserve lens shape, and preparation for scanning electron microscopy (SEM). SEM images were collected from the outer cortex to the nucleus, and fiber cell end-to-end curvature and membrane paddle dimensions were measured using ImageJ.</p><p><strong>Results: </strong>At 23% and 29% axial strain, cortical fiber bundle curvature increased significantly compared to control uncompressed lenses, whereas nuclear fiber bundle curvature was unaffected. Outer cortical fiber cell membrane paddles and protrusions were dramatically distorted in a radial direction, with loss of paddle-associated small protrusions in compressed lenses compared to controls, but nuclear fiber cell morphologies were unchanged. The compression-induced increases in cortical fiber cell curvature and distortion of membrane paddles were reversible, with fiber cell morphologies returning to those of control lenses after the release of load.</p><p><strong>Conclusions: </strong>Whole lens shape changes due to an increase in axial strain result in increased fiber cell curvature and distorted membrane morphologies in cortical but not nuclear fiber cells, indicating that mechanical strain dissipates with depth. The recovery of normal cortical fiber cell curvature and membrane morphologies after the removal of load and lens rounding back to its original shape suggests elastic properties of the young and mature fiber cells and their membrane paddles.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"53"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}