Fanxiu Xiong, Benjamin F Arnold, Thomas M Lietman, John A Gonzales
{"title":"Predictors of Discordance Between Dry Eye Symptoms and Signs: Insights From the Sjögren's International Collaborative Clinical Alliance.","authors":"Fanxiu Xiong, Benjamin F Arnold, Thomas M Lietman, John A Gonzales","doi":"10.1167/iovs.65.12.3","DOIUrl":"10.1167/iovs.65.12.3","url":null,"abstract":"<p><strong>Purpose: </strong>The diagnosis and management of dry eye disease (DED) could be complicated by the discordance between DED-related symptoms and signs. We performed a cross-sectional study to investigate the factors of and develop predictive models for the discrepancy in DED symptomatology.</p><p><strong>Methods: </strong>We used data from 3455 participants, 21 to 89 years old, from the Sjögren's International Collaborative Clinical Alliance study. We performed a multivariable stepwise linear regression model with backward elimination and Bayesian information criteria to select predictors for the discordance in DES symptomatology, which was defined as the difference between the rank score of Ocular Surface Disease Index 6 (OSDI-6) and the rank score of ocular staining score (OSS).</p><p><strong>Results: </strong>Ten predictors, such as \"vitality,\" \"immunomodulating drugs,\" sensory symptoms,\" and \"ethnicity,\" remained in the final models, achieving an adjusted R2 (aR2) of 0.35 (95% confidence interval [CI], 0.32-0.39). Specifically, medication use explained 19% (95% CI, 0.17-0.22) of the variance in the outcome, followed by medical history (aR2 = 0.18; 95% CI, 0.15-0.21). Health-related quality of life contributed 16% to the variance in the outcome (95% CI, 0.13-0.19), and, last, demographics contributed 11% (95% CI, 0.09-0.13).</p><p><strong>Conclusions: </strong>Our results suggest that individuals of Asian descent and those using immunomodulating medications often present with severe ocular signs that necessitate regular ophthalmological evaluations, even in the absence of proportionate ocular symptoms. Additionally, ocular symptoms, when accompanied by abnormal sensations in other parts of the body, could indicate systemic conditions that require further investigation and medical care.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371859","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}
Sina Bahrpeyma, Paulina Jakubiak, Rubén Alvarez-Sánchez, Antonello Caruso, Monika Leuthardt, Claudia Senn, Eva M Del Amo, Arto Urtti
{"title":"Comprehensive Pharmacokinetic Evaluation of High Melanin Binder Levofloxacin in Rabbits Shows Potential of Topical Eye Drops for Posterior Segment Treatment.","authors":"Sina Bahrpeyma, Paulina Jakubiak, Rubén Alvarez-Sánchez, Antonello Caruso, Monika Leuthardt, Claudia Senn, Eva M Del Amo, Arto Urtti","doi":"10.1167/iovs.65.12.14","DOIUrl":"10.1167/iovs.65.12.14","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this work was to understand the impact of melanin binding on ocular pharmacokinetics after administration of a high-binder model drug via different administration routes.</p><p><strong>Methods: </strong>We applied levofloxacin to pigmented and albino rabbits as eye drops (single and multiple), as well as by intravitreal and intravenous injections. Ocular tissues and plasma were analyzed for levofloxacin concentrations with liquid chromatography-mass spectrometry (LC-MS/MS), and pharmacokinetic parameters were calculated.</p><p><strong>Results: </strong>The data show enrichment of levofloxacin and weeks-long retention in pigmented tissues. Upon intravitreal injection, the area under the curve (AUC) values in pigmented tissues were about 9 to 15 times higher than the respective values in the albino rabbits, but this difference expanded to 255- to 951-fold following topical eye drop administration. Multiple dosing of eye drops led to substantial accumulation of levofloxacin in the pigmented tissues: AUC values were 3 to 12 times higher than after intravitreal injection. The AUCs were much lower after single topical or intravenous drug administrations. High drug levels (0.1-35 µM) were always observed in the neural retinas of pigmented eyes; the highest exposure was seen after intravitreal administration followed by multiple doses of topical drops. Single topical instillation and intravenous injections to the albino rabbits resulted in vitreal bioavailability values of 0.009% and 0.003%, respectively.</p><p><strong>Conclusions: </strong>Melanin binding can be used to achieve targeted drug delivery and extended retention in pigmented ocular tissues. The results from topical multiple dosing experiments suggest that eye drop treatment may yield drug exposures and responses comparable to intravitreal delivery, even in the retinal pigment epithelium and choroid.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390588","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":"Roflumilast Attenuates Microglial Senescence and Retinal Inflammatory Neurodegeneration Post Retinal Ischemia Reperfusion Injury Through Inhibiting NLRP3 Inflammasome.","authors":"Chunlian Ou, Yiwei Lin, Jing Wen, Hongyang Zhang, Ying Xu, Naiyuan Zhang, Qiong Liu, Yingzi Wu, Jing Xu, Jing Wu","doi":"10.1167/iovs.65.12.38","DOIUrl":"https://doi.org/10.1167/iovs.65.12.38","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal ischemia-reperfusion (RIR) injury is implicated in various retinal diseases, leading to retinal ganglion cells (RGCs) degeneration. Microglial senescence exacerbates inflammation, contributing to neurodegeneration. This study aimed to investigate the potential therapeutic role of Roflumilast (Roflu) in ameliorating microglial senescence and neuroinflammation following RIR injury.</p><p><strong>Methods: </strong>C57BL/6J mice underwent RIR surgery, and Roflu treatment was administered intraperitoneally. BV2 microglial cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to simulate ischemic conditions in vitro. SA-β-gal staining was used to detect cellular senescence. Quantitative PCR and ELISA were used to examine the levels of senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin (H&E) staining was performed on retinal sections to assess retinal morphology and thickness. Surviving RGCs were labeled and quantified in retinal whole-mounts using immunofluorescence (IF). Furthermore, Western blot and IF staining were used to quantify the proteins associated with the cell cycle and NLRP3 inflammasomes.</p><p><strong>Results: </strong>Roflu treatment reduced microglial senescence, ROS production, and secretion of pro-inflammatory cytokines in OGD/R-exposed BV2 cells. It also restored cell proliferation capacity and reversed OGD/R-induced cell cycle arrest. In vivo, Roflu alleviated retinal senescence, preserved retinal thickness, and protected against RGCs death in the RIR mouse model. Mechanistically, Roflu inhibited the NLRP3 inflammasome activation and suppressed DNA damage signaling pathway in microglia.</p><p><strong>Conclusions: </strong>Roflu exerts neuroprotective effects by mitigating microglial senescence and inflammation via inhibition of the NLRP3 inflammasome in RIR injury. These findings suggest that Roflu may serve as a promising therapeutic strategy for retinal diseases associated with ischemic injury by targeting microglial senescence.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500610","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}
Samuel David Giesser, Ferhat Turgut, Amr Saad, Chiara Sommer, Yukun Zhou, Siegfried Karl Wagner, Pearse Andrew Keane, Matthias Becker, Delia Cabrera DeBuc, Gábor Márk Somfai
{"title":"A New Retest-Stable Tortuosity Metric for Retinal Vessel Analyses.","authors":"Samuel David Giesser, Ferhat Turgut, Amr Saad, Chiara Sommer, Yukun Zhou, Siegfried Karl Wagner, Pearse Andrew Keane, Matthias Becker, Delia Cabrera DeBuc, Gábor Márk Somfai","doi":"10.1167/iovs.65.12.30","DOIUrl":"10.1167/iovs.65.12.30","url":null,"abstract":"<p><strong>Purpose: </strong>Existing retinal vessel tortuosity metrics lack standardization and retest reliability, hindering their clinical utility. Our study addresses this gap by introducing a novel metric, coined as the \"vascular curvature index\" (VCI), to enhance accuracy and consistency in biomarkers associated with medical conditions. We assess VCI's performance in terms of retest reliability in healthy subjects to transform early detection and monitoring approaches for various diseases.</p><p><strong>Methods: </strong>We recruited 44 patients for a single-session study, capturing fundus images before and after a five-minute break. Using AutoMorph, we generated vessel segmentation maps and evaluated retest reliability using multiple tortuosity metrics. The VCI was introduced and statistically compared to existing metrics. We performed a paired one-sided t-test to test for significantly improved retest reliability of our newly proposed metric. We analyzed distribution histograms, Fisher-Pearson coefficient of skewness, and correlation matrices for further insights.</p><p><strong>Results: </strong>VCI is the most retest-reliable metric, statistically surpassing other curvature metrics, except inverse spherical radius tortuosity. With a somewhat negatively distributed pattern (coefficient of skewness of -0.52), VCI exhibits the strongest correlation with the second most retest-reliable metric; inverse-radius-tortuosity (Pearson and Spearman correlation of 0.7 and 0.72, respectively). Its correlation with angle-tortuosity is lower (Pearson and Spearman correlation of 0.05 and 0.07, respectively).</p><p><strong>Conclusions: </strong>The VCI emerges as a highly retest-reliable metric with a relatively normal distribution in healthy patients. Further investigation is warranted to evaluate its clinical performance in real-world applications, potentially influencing proactive healthcare interventions and personalized treatment decision-making.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465667","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}
Joshua N Dang, Jolan Wu, Yujiao Zheng, Jason J Bunk, Emily K Tam, Karen E Lee, Sumner E Lawson, Tatiana R Monger, Alex T Legocki, John P Kelly, Obiageri Egeolu, Leona Ding, Ruikang K Wang, Kristina Tarczy-Hornoch, Michelle T Cabrera
{"title":"Semi-Automated Analysis of Dome-Shaped Macula in Preterm and Full-Term Infants Using Handheld Swept-Source Optical Coherence Tomography.","authors":"Joshua N Dang, Jolan Wu, Yujiao Zheng, Jason J Bunk, Emily K Tam, Karen E Lee, Sumner E Lawson, Tatiana R Monger, Alex T Legocki, John P Kelly, Obiageri Egeolu, Leona Ding, Ruikang K Wang, Kristina Tarczy-Hornoch, Michelle T Cabrera","doi":"10.1167/iovs.65.12.35","DOIUrl":"https://doi.org/10.1167/iovs.65.12.35","url":null,"abstract":"<p><strong>Purpose: </strong>Dome-shaped macula (DSM) is known to occur in highly myopic adults and, recently, preterm infants. This study uses investigational handheld swept-source optical coherence tomography (SS-OCT) to further characterize infantile DSM.</p><p><strong>Methods: </strong>In this prospective, observational study, preterm infants undergoing retinopathy of prematurity screening and full-term infants within 72 hours of birth were imaged. Two trained graders assessed macular features, including DSM, subretinal fluid, and macular edema. A semi-automated program measured foveal immaturity, dome height, and diameter.</p><p><strong>Results: </strong>Two hundred seventeen imaging sessions from 50 full-term and 30 preterm infants were included (46% female, preterm birth weight 1038 ± 335 g, and gestational age 28.7 ± 3.1 weeks). DSM occurred in 40% preterm versus 14% full-term infants (P = 0.01). Mean postmenstrual age at first DSM diagnosis was 38.4 ± 0.0 weeks among preterm and 40.4 ± 1.1 weeks among full-term infants (P < 0.001). Dome height and diameter measured 55.67 ± 44.22 µm and 3583.15 ± 1090.35 µm for preterm versus 88.37 ± 44.73 µm and 3581.97 ± 355.07 µm for full-term infants (P = 0.24 and P = 0.96, respectively). All 27 images (11 preterm and 7 full-term infants) with 3-dimensional analysis had round dome configuration. No other associations were seen, including macular fluid (P = 0.17).</p><p><strong>Conclusions: </strong>Infants frequently exhibit DSM without an association with macular fluid. Preterm infants were more likely than full-term infants to have DSM. Unlike DSM in children and adults, infantile DSM configuration is mostly round rather than ridge-shaped.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500611","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}
Peter S Stewart, Bindi S Brook, Oliver E Jensen, Tamsin A Spelman, Robert J Whittaker, Moussa A Zouache
{"title":"Rapid Amplification of Cerebrospinal Fluid Pressure as a Possible Mechanism for Optic Nerve Sheath Bleeding in Infants With Nonaccidental Head Injury.","authors":"Peter S Stewart, Bindi S Brook, Oliver E Jensen, Tamsin A Spelman, Robert J Whittaker, Moussa A Zouache","doi":"10.1167/iovs.65.12.9","DOIUrl":"10.1167/iovs.65.12.9","url":null,"abstract":"<p><strong>Purpose: </strong>Subdural hemorrhage along the optic nerve (ON) is a histopathological indicator of abusive head trauma (AHT) in infants. We sought to determine if this bleeding could be caused by an abrupt increase in intracranial pressure transmitted to cerebrospinal fluid (CSF) at the optic foramen (OF).</p><p><strong>Methods: </strong>A theoretical model is developed to simulate the effect of a pressure perturbation of maximal amplitude P applied at the optic foramen for a short duration T on the CSF-filled ON subarachnoid space (ONSAS). The ONSAS is modelled as a fluid-filled channel with an elastic wall representing the flexible ONSAS-arachnoid/dura interface. A constitutive law describing the relationship between CSF pressure and ONSAS deformation is inferred from published measurements. CSF pressure profiles along the ONSAS are examined systematically over a broad range of P and T.</p><p><strong>Results: </strong>The pressure perturbation initiated at the OF produces a pressure wave that stretches the ONSAS. This wave propagates rapidly along the ONSAS toward the scleral end of the ON, where it is reflected back toward the brain. For sufficiently small T a shock wave with amplification up to six times larger than P over a timescale of tens of milliseconds is observed at the scleral end of the ON. Comparatively smaller amplifications are observed for slower perturbations.</p><p><strong>Conclusions: </strong>A sudden increase in CSF pressure in the cranial cavity can cause a rapid expansion of the ONSAS, which may lead to rupture of the bridging blood vessels. Our study predicts a plausible mechanism for subdural hemorrhage that occurs in abusive head trauma in infants.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380769","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}
Yong Woo Kim, Glen P Sharpe, Julia Siber, Ralf Keßler, Jörg Fischer, Tilman Otto, Balwantray C Chauhan
{"title":"Critical Impact of Working Distance on OCT Imaging: Correction of Optical Distortion and Its Effects on Measuring Retinal Curvature.","authors":"Yong Woo Kim, Glen P Sharpe, Julia Siber, Ralf Keßler, Jörg Fischer, Tilman Otto, Balwantray C Chauhan","doi":"10.1167/iovs.65.12.10","DOIUrl":"10.1167/iovs.65.12.10","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the impact of working distance (WD) on optical distortion in optical coherence tomography (OCT) imaging and to evaluate the effectiveness of optical distortion correction in achieving consistent retinal Bruch's membrane (BM) layer curvature, regardless of variations in WD.</p><p><strong>Methods: </strong>Ten subjects underwent OCT imaging with four serial macular volume scans, each employing distinct WD settings adjusted by balancing the sample and reference arm of the OCT interferometer (eye length settings changed). Either of two types of 30° standard objectives (SOs) was used. A ray tracing model was used to correct optical distortion, and BM layer curvature (represented as the second derivative of the curve) was measured. Linear mixed effects (LME) modeling was used to analyze factors associated with BM layer curvature, both before and after distortion correction.</p><p><strong>Results: </strong>WD exhibited significant associations with axial length (β = -1.35, P < 0.001), SO type (P < 0.001), and eye length settings (P < 0.001). After optical distortion correction, the mean ± SD BM layer curvature significantly increased from 16.80 ± 10.08 µm-1 to 49.31 ± 7.50 µm-1 (P < 0.001). The LME model showed a significant positive association between BM layer curvature and WD (β = 1.94, P < 0.001). After distortion correction, the percentage change in BM layer curvature due to a 1-mm WD alteration decreased from 9.75% to 0.25%.</p><p><strong>Conclusions: </strong>Correcting optical distortion in OCT imaging significantly mitigates the influence of WD on BM layer curvature, enabling a more accurate analysis of posterior eye morphology, especially when variations in WD are unavoidable.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380867","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}
Guifang Wang, Yujie Zhu, Yuzhen Liu, Mulin Yang, Li Zeng
{"title":"Mesenchymal Stem Cells-Derived Exosomal miR-223-3p Alleviates Ocular Surface Damage and Inflammation by Downregulating Fbxw7 in Dry Eye Models.","authors":"Guifang Wang, Yujie Zhu, Yuzhen Liu, Mulin Yang, Li Zeng","doi":"10.1167/iovs.65.12.1","DOIUrl":"10.1167/iovs.65.12.1","url":null,"abstract":"<p><strong>Purpose: </strong>Our previous study indicated that exosomes derived from mouse adipose-derived mesenchymal stem cells (mADSC-Exos) alleviated the benzalkonium chloride (BAC)-induced mouse dry eye model. However, the specific active molecules in mADSC-Exos that contribute to anti-dry eye therapy remain unidentified. In this study, we aimed to investigate the efficacy and mechanisms of miR-223-3p derived from mADSC-Exos in dry eye models.</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to determine miR-223-3p derived from mADSC-Exos that exerted anti-inflammatory effects on hyperosmolarity-induced mouse corneal epithelial cells (MCECs). The therapeutic efficacy of miR-223-3p was evaluated in mice with dry eye induced by either BAC or scopolamine (Scop). Mice were randomly assigned to 5 groups: sham, model, miR-223-3p overexpression, miR-223-3p knockdown, and 0.1% pranoprofen (positive group). Post-treatment, the severity of dry eye symptoms, and the pro-inflammatory cytokine levels were assessed. The effect of miR-223-3p on silencing the target gene was verified using ELISA and dual luciferase reporter assays.</p><p><strong>Results: </strong>The mADSC-Exos that knocked out miR-223-3p did not reduce interleukin (IL)-6 content. Supplementing with miR-223-3p could restore the reduction of IL-6. The miR-223-3p effectively ameliorated ocular surface damage and decreased pro-inflammatory cytokines or chemokines in both BAC- and Scop-induced mouse dry eye models. Furthermore, miR-223-3p inhibited cell apoptosis. F-box and WD repeat domain-containing 7 (Fbxw7) was the potential direct target of miR-223-3p. The miR-223-3p suppressed the 3'-untranslated region of Fbxw7. The Fbxw7 knockdown suppressed hyperosmolarity-induced inflammation in MCECs.</p><p><strong>Conclusions: </strong>The mADSC-derived exosomal miR-223-3p mitigates ocular surface damage and inflammation, indicating its potential as a promising treatment option for dry eye.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346863","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}
Tao Tang, Chi Ren, Yi Cai, Yan Li, Kai Wang, Mingwei Zhao
{"title":"Lifelong Changes in the Choroidal Thickness, Refractive Status, and Ocular Dimensions in C57BL/6J Mouse.","authors":"Tao Tang, Chi Ren, Yi Cai, Yan Li, Kai Wang, Mingwei Zhao","doi":"10.1167/iovs.65.12.26","DOIUrl":"10.1167/iovs.65.12.26","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the changes in choroidal thickness (ChT), refractive status, and ocular dimensions in the mouse eye in vivo using updated techniques and instrumentation.</p><p><strong>Methods: </strong>High-resolution swept-source optical coherence tomography (SS-OCT), eccentric infrared photoretinoscopy, and custom real-time optical coherence tomography were used to analyze choroidal changes, refractive changes and ocular growth in C57BL/6J mice from postnatal day (P) 21 to month 22.</p><p><strong>Results: </strong>The ChT gradually increased with age, with the thickest region in the para-optic nerve head and thinning outward, and the temporal ChT was globally thicker than the nasal ChT. Retinal thickness remained stable until 4 months and subsequently decreased. The average spherical equivalent refraction error was -4.81 ± 2.71 diopters (D) at P21, which developed into emmetropia by P32, reached a hyperopic peak (+5.75 ± 1.38 D) at P82 and returned to +0.66 ± 1.86 D at 22 months. Central corneal thickness, anterior chamber depth, lens thickness, and axial length (AL) increased continuously before 4 months, but subsequently exhibited subtle changes. Vitreous chamber depth decreased with lens growth. ChT was correlated significantly with the ocular parameters (except for retinal thickness) before the age of 4 months, but these correlations diminished after 4 months. Furthermore, for mice younger than 4 months, the difference in the ChT, especially temporal ChT, between the two eyes contributed most to that of axial length and spherical equivalent refraction error.</p><p><strong>Conclusions: </strong>Four months could be a watershed age in the growth of mouse eyes. Large-span temporal recordings of refraction, ocular dimensions, and choroidal changes provided references for the study of the physiological and pathological mechanisms responsible for myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465682","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}
Beverly A Karpinski, Sonali Pal-Ghosh, Himani Datta-Majumdar, Shelly Dimri, Soneha Datta, Mary Ann Stepp
{"title":"ROCK Inhibitor Enhances Neurite Outgrowth In Vitro and Corneal Sensory Nerve Reinnervation In Vivo.","authors":"Beverly A Karpinski, Sonali Pal-Ghosh, Himani Datta-Majumdar, Shelly Dimri, Soneha Datta, Mary Ann Stepp","doi":"10.1167/iovs.65.12.31","DOIUrl":"10.1167/iovs.65.12.31","url":null,"abstract":"<p><strong>Purpose: </strong>The intraepithelial corneal nerves are essential to corneal health. Rho kinase or ROCK inhibitors (RIs) have been reported to play a role in neuron survival after injury. Here we assess integrin and extracellular matrix expression in primary mouse neurons and determine whether treating cells with RI impacts neurite outgrowth in vitro and reinnervation after trephine and debridement injury in mice in vivo.</p><p><strong>Methods: </strong>Cocultures of human corneal limbal epithelial cells and E11.5 mouse trigeminal neurons and neurons alone were grown on glass coverslips. High-resolution imaging was performed to localize integrins and laminin on neurons and to determine whether RI impacts neurite outgrowth in vitro and in vivo after both 1.5-mm trephine and 1.5-mm debridement injuries.</p><p><strong>Results: </strong>Several integrin α (α3, α6, αv) chains as well as β4 integrin are expressed on neuron axons and growth cones in cocultures. RI treatment of isolated neurons, cocultures, and in conditioned media increases neurite outgrowth. In vivo, RI positively impacts sensory nerve reinnervation after trephine and debridement injury.</p><p><strong>Conclusions: </strong>These studies are the first to demonstrate expression of β4 integrin on trigeminal sensory neurons and preferential adhesion of neurons to the laminin-enriched matrices found in footprints deposited by human corneal limbal epithelial cells. In addition, we also document for the first time the positive impact of RI on neurite outgrowth in vitro and reinnervation in vivo.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465686","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}