Morin reverses P-glycoprotein-mediated multidrug-resistance in KBChR-8-5 cancer cell lines.

Multidrug resistance (MDR) during clinical chemotherapy for cancer has been considered a major obstacle to treatment efficacy. The involvement of adenosine triphosphate-binding cassette (ABC) transporters in the MDR mechanism significantly reduces the efficacy of chemotherapeutics. This study investigates the potential of morin, a dietary bioflavonoid, to overcome colchicine resistance in KBChR-8-5 MDR cells. The P-gp inhibitory activity by morin was measured by calcein-AM drug efflux assay. Western blot analysis was employed to evaluate P-gp messenger RNA and protein expressions following morin treatment. Flow cytometry analysis and acridine orange/ethidium bromide fluorescence staining were utilised to investigate the induction of apoptosis and cell cycle arrest upon treatment with morin and paclitaxel in combination. Additionally, polymerase chain reaction (PCR) array analysis was conducted to study the gene expression profiles related to MDR, apoptosis and cell cycle arrest during treatment with morin, paclitaxel or their combination. Morin exhibited a strong binding interaction with human P-gp. This was corroborated by drug efflux assays, which showed a reduction in P-gp efflux function with increasing morin concentration. Furthermore, morin and paclitaxel combination potentiated the induction of apoptosis and G2/M phase cell cycle arrest. Morin treatment significantly downregulated the gene expression of ABCB1 and P-gp membrane expressions in MDR cells. Additionally, PCR array gene expression analysis revealed that the combination treatment with morin and paclitaxel upregulated proapoptotic and cell cycle arrest genes while downregulating ABCB1 gene and antiapoptotic genes. Thus, morin effectively reversed paclitaxel resistance in KBChR-8-5 drug-resistant cancer cells and concluded that morin resensitized the paclitaxel resistance in KBChR8-5 drug-resistant cancer cells.

The features of serous retinal detachment in preeclampsia viewed on spectral-domain optical coherence tomography.

OBJECTIVE: To evaluate the characteristics of serous retinal detachment on spectral-domain optical coherence tomography in preeclampsia. METHODS: In this retrospective case-series study, clinical characteristics of retinal damage were evaluated using spectral-domain optical coherence tomography (SD-OCT) imaging. RESULTS: Thirty affected eyes from 16 pregnant women with preeclampsia were included. The features of serous retinal detachment, observed using SD-OCT, consisted of lesions located in the macular or peripapillary region; the presence of intraretinal or subretinal fluid (intraretinal fluid, IRF; subretinal fluid, SRF); ellipsoid zone integrity (normal/abnormal); intraretinal hyper-reflective dots; and Elschnig spots (retinal pigment epithelium lesions). Of the 30 affected eyes, 25 (83.33%) had lesions located in the macular region, 19 (63.33%) outside the macula (in the peripapillary region), and 14 (46.67%) in both. SD-OCT showed IRF in 2 eyes (6.67%), SRF in 30 eyes (100.00%), and both in 2 eyes (6.67%). The ellipsoid zone was disrupted in 20 eyes (66.67%), intraretinal hyper-reflective dots were observed in 4 eyes (13.33%), and Elschnig spots were observed in 20 eyes (66.67%). CONCLUSION: Spectral-domain optical coherence tomography is a non-invasive, reliable imaging tool for the assessment of retinal pathologies in preeclampsia.

The integrated transcriptome bioinformatics analysis identifies key genes and cellular components for proliferative diabetic retinopathy.

Proliferative Diabetic Retinopathy (PDR) is a chronic complication of Diabetes and the main cause of blindness among the world's working population at present. While there have been many studies on the pathogenesis of PDR, its intrinsic molecular mechanisms have not yet been fully elucidated. In recent years, several studies have employed bulk RNA-sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to profile differentially expressed genes (DEGs) and cellular components associated with PDR. This study adds to this expanding body of work by identifying PDR's target genes and cellular components by conducting an integrated transcriptome bioinformatics analysis. This study integrately examined two public bulk RNA-seq datasets(including 11 PDR patients and 7 controls) and one single-cell RNA-seq datasets(including 5 PDR patients) of Fibro (Vascular) Membranes (FVMs) from PDR patients and control. A total of 176 genes were identified as DEGs between PDR patients and control among both bulk RNA-seq datasets. Based on these DEGs, 14 proteins were identified in the protein overlap within the significant ligand-receptor interactions of retinal FVMs and Protein-Protein Interaction (PPI) network, three of which were associated with PDR (CD44, ICAM1, POSTN), and POSTN might act as key ligand. This finding may provide novel gene signatures and therapeutic targets for PDR.

Effects of varying illumination on ocular aberrations and aberration compensation before and after small incision Lenticule extraction: a prospective cohort study.

BACKGROUND: There are few reports regarding the influence of varying illumination on the compensation effect before and after corneal refractive surgery. We aimed to evaluate the changes in refraction, higher-order aberrations, and aberration compensation between mesopic and photopic illumination before and after small incision lenticule extraction. METHODS: In this prospective cohort study, only the right eyes of patients who underwent small incision lenticule extraction for the correction of myopia and myopic astigmatism at the Tianjin Eye Hospital were included. Wavefront refraction and higher-order aberrations were measured preoperatively and 3 months postoperatively under mesopic and photopic illumination. Compensation factors were calculated as 1 - (aberration of the whole eye/aberration of the anterior corneal surface). RESULTS: Forty patients undergoing small incision lenticule extraction were enrolled. All surgeries were completed without postoperative complications. Preoperatively, the eyes only had a statistically significantly higher (t = - 4.589, p < .001) spherical refractive error under mesopic vs. photopic illumination (median [interquartile range], - 6.146 [2.356] vs. - 6.030 [2.619] diopters [D]), whereas postoperatively, the eyes also exhibited statistically significantly higher (t = - 3.013, p = .005) astigmatism (- 0.608 [0.414] vs. - 0.382 [0.319] D). Differences in spherical refraction between the two illuminations were the highest in postoperative eyes (Δ > 0.5 D). Only postoperative eyes exhibited statistically significant elevations (t ≥ 4.081, p < .001) in higher-order aberrations under mesopic illumination, and only preoperative eyes exhibited statistically significantly enhanced (χ2 = 6.373, p = .01 for fourth-order and χ2 = 11.850, p = .001 for primary spherical aberrations) and decreased (χ2 = 13.653, p = .001 for horizontal trefoil) compensation factors under mesopic illumination. CONCLUSIONS: Exaggerations in higher-order aberrations and myopic shift after small incision lenticule extraction became apparent under mesopic illumination. Slight undercorrection may have an enhanced effect under low illumination and may reduce night vision. The specific changes in compensation effects in preoperative eyes may improve optical quality under mesopic illumination. Postoperative eyes have reduced compensation ability, specifically for spherical aberrations, under mesopic illumination, which may diminish night vision. Further studies that include the measurement of subjective night vision parameters should be conducted.

Effect of Wavefront Aberrations on Night Vision Problems and Mesopic Contrast Threshold After SMILE.

PURPOSE: To investigate the effect of wavefront aberrations on night vision problems and mesopic contrast threshold after small incision lenticule extraction (SMILE). METHODS: Forty-two participants (84 eyes) who underwent SMILE were included in this prospective observational study. Visual outcomes including uncorrected distance visual acuity (UDVA), subjective manifest refraction, mesopic contrast threshold (Binoptometer 4P; Oculus Optikgeräte GmbH), and higher order aberrations (HOAs) were analyzed before and 3 months after surgery. The patient's night vision satisfaction was assessed using a questionnaire. RESULTS: The mean spherical equivalent was -5.30 ± 1.38 diopters (D) preoperatively and -0.06 ± 0.15 D postoperatively. UDVA was better than 20/20 in 98.81% of the patients and better than 20/25 in all patients. Scores of night vision satisfaction and glare changed significantly in the postoperative period (F = 8.463, P = .001; F = 69.518, P < .001, respectively). Preoperative spherical diopters (lower order aberrations) were positively correlated with night vision satisfaction (r = -0.329, P = .041) and glare score (r =-0.332, P = .039). Age (odds ratio [OR] = 1.272, 95% CI = 1.019 to 1.589) and preoperative spherical diopter (OR = 0.437, 95% CI = 0.199 to 0.975) were correlated with night vision satisfaction scores by analysis of binary regression. The root mean square value of total HOAs increased 3 months after surgery (t = -6.873, P < .001) with an increase in horizontal coma (Z31) and spherical aberration (Z40) (P < .001). No correlation was observed between glare score and HOAs; however, patients with higher preoperative myopia demonstrated continuously decreasing contrast under mesopic conditions and higher postoperative horizontal coma. CONCLUSIONS: Myopic patients with higher preoperative spherical errors experienced more glare at night after SMILE surgery. Postoperative horizontal coma was associated with worse mesopic contrast thresholds. [J Refract Surg. 2021;37(7):446-452.].

Quantitative Evaluation of Aerosol Generation from Non-contact Tonometry and its Correlation with Tear Film Characteristics.

INTRODUCTION: Ophthalmologists are inevitably exposed to tears and ocular discharge during ophthalmologic examinations and are at high risk for SARS-CoV-2 infection. To understand the role of aerosols in disease transmission, we adopted a prospective cross-sectional study design and investigated the count and size distribution of aerosols generated by a non-contact tonometer and its correlation with individual tear film characteristics. METHODS: This study constituted two parts. The study population included outpatients who underwent an intraocular pressure examination in an intraocular pressure examination room (Part I) and 20 participants who underwent an intraocular pressure examination in a laboratory (Part II). The following main outcomes were measured: aerosol counts at 0, 50, 100, 150, and 200 cm from the non-contact tonometer (Part I); aerosol counts after each participant underwent non-contact tonometry, and lipid layer thickness score and tear film break-up time (Part II). RESULTS: The aerosol count decreased with increasing distance from the tonometer. The aerosol count at 0 cm had the highest value compared to that at other distances. For aerosols of diameters 0.25-0.5 µm and 0.5-1.0 µm, the count decreased at 50 cm and remained stable at further distances. For aerosols of diameters 1.0-2.5 µm and ≥ 2.5 µm, the count dropped progressively at all five distances. The aerosol count from each tonometer correlated positively with the lipid layer thickness score (r = 0.490, P = 0.028), whereas the aerosol count correlated negatively with the tear film break-up time (r = - 0.675, P = 0.001). CONCLUSIONS: Aerosols tended to coagulate during diffusion. A 50-cm distance from the tonometer could confer safety from aerosols with < 1.0-µm diameter. Aerosols generated during non-contact tonometry could contain a lipid layer component. Moreover, tear film stability could affect aerosol generation. Protective eyewear is recommended for reducing infection risk from aerosols. Individual tear film characteristics should be considered during non-contact tonometry.

The Effect of Intraoperative Angle Kappa Adjustment on Higher-Order Aberrations Before and After Small Incision Lenticule Extraction.

PURPOSE: To compare higher-order aberrations (HOAs) after small incision lenticule extraction (SMILE) in patients with and without intraoperative angle kappa adjustments. METHODS: This is a retrospective case series. One hundred six eyes of 106 patients who underwent SMILE at Tianjin Eye Hospital (Tianjin Medical University, Tianjin, China) for correction of myopia and myopic astigmatism were divided into 2 groups. The first group consisted of eyes with intraoperative angle kappa adjustment and the second group consisted of eyes without adjustment. Preoperative and postoperative visual outcome, refraction, and HOA measurements at 1 and 3 months were compared. RESULTS: At the pupil size of 6 mm, vertical coma at 1 and 3 months after SMILE for the angle kappa-adjusted group was 0.153 ± 0.107 and 0.157 ± 0.094 µm, which were significantly lower than those of the nonadjusted group (0.204 ± 0.117 and 0.203 ± 0.113 µm, respectively) (P = 0.026 at 1 mo, P = 0.047 at 3 mo). The change in vertical coma between preoperative and postoperative measurements was 0.011 ± 0.136 and 0.023 ± 0.129 µm at 1 and 3 months postoperatively for the angle kappa-adjusted group, which were lower than those of the nonadjusted group (0.082 ± 0.165 and 0.085 ± 0.150 µm, respectively) (P = 0.023 at 1 mo, P = 0.045 at 3 mo). Subgroup analysis for eyes with large angle kappa demonstrated that the vertical coma was significantly less in the angle kappa-adjusted group at both 1 and 3 months (P = 0.009, P = 0.043, respectively). No significant correlation was observed between angle kappa and HOAs in the angle kappa-adjusted group. CONCLUSIONS: Adjustment of angle kappa during SMILE resulted in less HOAs. It would provide more insight on how to optimize treatment centration in SMILE.

Comparative analysis of biomechanically corrected intraocular pressure with corneal visualization Scheimpflug technology versus conventional noncontact intraocular pressure.

PURPOSE: To compare the difference between biomechanically corrected intraocular pressure (bIOP) and noncontact IOP measurement (IOPNCT) and to investigate the effect of corneal biomechanical properties on IOP. METHODS: IOP was evaluated in 1046 myopic eyes (544 subjects) using a conventional noncontact tonometer and a novel corneal visualization Scheimpflug technology (Corvis ST). Corneal biomechanical parameters were measured using the Corvis ST. RESULTS: The mean IOPNCT and bIOP values were significantly different (15.59 ± 2.56 mmHg and 15.89 ± 1.75 mmHg, respectively; P < 0.001). The bIOP showed a less correlation with central corneal thickness (CCT), compared with IOPNCT (P < 0.01). The IOPNCT was lower than the bIOP when the thickness of cornea was ≤ 550 µm but higher than bIOP when it was ≥ 550 µm (P < 0.01). A strong association was found between IOPNCT and deflection amplitude and deflection area at the highest concavity (HC DefA and HC DefArea), stiff parameter, maximum deformation amplitude (DAmax), and maximum deflection amplitude (DefAmax), as well as for bIOP (r > 0.500, P < 0.001). The bIOP could be calculated based on IOPNCT according to different values of CCT (P < 0.01). CONCLUSIONS: The bIOP was less affected by CCT as compared to IOPNCT. IOPNCT may be underestimated when the cornea is thinner and overestimated when the cornea is thicker because of the difference in corneal biomechanics.

Applying Machine Learning Techniques in Nomogram Prediction and Analysis for SMILE Treatment.

PURPOSE: To analyze the outcome of machine learning technique for prediction of small incision lenticule extraction (SMILE) nomogram. DESIGN: Prospective, comparative clinical study. METHODS: A comparative study was conducted on the outcomes of SMILE surgery between surgeon group (nomogram set by surgeon) and machine learning group (nomogram predicted by machine learning model). The machine learning model was trained by 865 ideal cases (spherical equivalent [SE] within ±0.5 diopter [D] 3 months postoperatively) from an experienced surgeon. The visual outcomes of both groups were compared for safety, efficacy, predictability, and SE correction. RESULTS: There was no statistically significant difference between the baseline data in both groups. The efficacy index in the machine learning group (1.48 ± 1.08) was significantly higher than in the surgeon group (1.3 ± 0.27) (t = -2.17, P < .05). Eighty-three percent of eyes in the surgeon group and 93% of eyes in the machine learning group were within ±0.50 D, while 98% of eyes in the surgeon group and 96% of eyes in the machine learning group were within ±1.00 D. The error of SE correction was -0.09 ± 0.024 and -0.23 ± 0.021 for machine learning and surgeon groups, respectively. CONCLUSIONS: The machine learning technique performed as well as surgeon in safety, but significantly better than surgeon in efficacy. As for predictability, the machine learning technique was comparable to surgeon, although less predictable for high myopia and astigmatism.

Real-Time Intraocular Pressure Measurements in the Vitreous Chamber of Rabbit Eyes During Small Incision Lenticule Extraction (SMILE).

PURPOSE: To investigate real-time intraocular pressure (IOP) during small incision lenticule extraction (SMILE) in rabbit eyes for myopia correction. METHODS: During SMILE, real-time IOP was measured in the vitreous cavity of rabbit eyes with an optic fiber pressure sensor (OFPS). Two groups (n = 6 for each) underwent surgery, one group for a -2.00 diopter (D) refractive spherical correction and the other for a -6.00 D correction. RESULTS: During surgery, the IOP increased once the glass contact attached to the cornea (Pre-suction), and peaked 83.94 mmHg (SD ± 23.87 mmHg) for the -2.00 D group and 89.17 mmHg (SD ± 22.66 mmHg) for the -6.00 D group, both average values were less than 110 mmHg when suction was initiated to fix the glass contact onto the cornea (Suction on). It then fell to 74.81 mmHg (SD ± 20.64 mmHg) and 76.94 mmHg (SD ± 27.43 mmHg), respectively, and remained stable during lenticule creation (Cutting). After suction stopped (Suction off), IOP fell steeply. During lenticule separation/extraction, the change in IOP was 32.26 mmHg (SD ± 2.91 mmHg). Notably, the average duration of elevated IOP during the surgery was 166.05 s (no longer than 3 min). CONCLUSIONS: The IOP fluctuations in the vitreous cavity using an OFPS in a rabbit model during SMILE showed that real-time IOP significantly was increased during Pre-suction, Suction on, Cutting, Suction off, and lenticule separation/extraction compared to baseline IOP, although, peaked at Suction on. Neither the degree of myopic correction nor central corneal thickness significantly affected these changes in IOP.