Transcriptomic Analysis of Retinal Gene in Experimental Retinal Detachment Rats and Exploration of S100A9 and TLR4 in Human Vitreous.

PURPOSE: To screen for the differentially expressed genes in experimental retinal detachment rats, and to explore the expression of S100 calcium-binding protein A9 and Toll-like receptor 4 in the vitreous of rhegmatogenous retinal detachment patients. METHODS: Three rats of experimental retinal detachment and three normal rats were enrolled in the study. Transcriptomics (RNAseq) sequencing technology was used to screen differentially expressed genes in the retinas of the experimental retinal detachment group and the normal group. The selected differentially expressed genes for gene ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed. In addition, the vitreous of 15 patients with rhegmatogenous retinal detachment and six patients with the control group were collected. The expressions of S100 calcium-binding protein A9 and Toll-like receptor 4 were detected by Elisa, and the differences in expression levels were analyzed statistically. RESULTS: A total of 198 differentially expressed genes were screened by RNAseq sequencing, including 118 upregulated genes and 80 downregulated genes. Kyoto Encyclopedia of Genes and Genomes analysis confirmed that the most enriched pathway was the mitogen-activated protein kinase signaling pathway. Compared to the normal group, the expressions of suppressor of cytokine signaling-3, Storkhead box-2, S100 calcium-binding protein A9, Spi-1 proto-oncogene, phosphodiesterase 1B, and kinesin-light chain 1 mRNA in the retinas of the experimental retinal detachment rats were up-regulated, and the expressions of Max interacting protein 1 and the voltage-gated sodium 1 were down-regulated. Compared to the control group, the expressions of S100 calcium-binding protein A9 and Toll-like receptor 4 were upregulated by Elisa in the vitreous humor of rhegmatogenous retinal detachment patients with a statistically significant difference (p all <.05). CONCLUSION: The differentially expressed genes of experimental retinal detachment rats were suppressor of cytokine signaling-3, Storkhead box-2, S100 calcium-binding protein A9, Spi-1 proto-oncogene, phosphodiesterase 1B, kinesin-light chain 1, Max interacting protein 1, voltage-gated sodium 1, etc. The differences of S100 calcium-binding protein A9 and Toll-like receptor 4 expressions between the rhegmatogenous retinal detachment patients and the control group were statistically significant, indicating that they may play a potential role in the inflammatory process of rhegmatogenous retinal detachment.

Circ-MKLN1/miR-377-3p/CTGF Axis Regulates the TGF-ß2-induced Posterior Capsular Opacification in SRA01/04 Cells.

OBJECTIVE: Posterior capsular opacification (PCO) is a common postoperative ocular complication after cataract surgery. Little research focused on the regulation of circular RNAs (circRNAs) in PCO. This study was designed to investigate the function of circRNA-muskelin (circ-MKLN1) in PCO. METHODS: SRA01/04 cells were treated with transforming growth factor (TGF)-ß2. Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay. Transwell assay was used for cell migration and invasion detection. Cell migration was also measured by wound healing assay. Epithelial-mesenchymal transition (EMT)-related proteins and connective tissue growth factor (CTGF) were quantified using western blot. RESULTS: Cell viability, migration, invasion and EMT process in SRA01/04 cells were facilitated by TGF-ß2. Circ-MKLN1 expression was enhanced in 17 PCO lens samples relative to 19 normal lens samples and TGF-ß2-treated SRA01/04 cells contrasted to control cells. Downregulation of circ-MKLN1 inhibited the effects of TGF-ß2 on SRA01/04 cells. Circ-MKLN1 targeted miR-377-3p and the regulation of si-circ-MKLN1 for the TGF-ß2-induced influences was related to the upregulation of miR-377-3p. CTGF was the target gene for miR-377-3p. CTGF knockdown also abolished the TGF-ß2-mediated cell growth, migration and invasion of SRA01/04 cells. The function of miR-377-3p was achieved by reducing the CTGF level. TGF-ß2-induced CTGF expression promotion was alleviated by si-circ-MKLN1 through upregulating the expression of miR-377-3p. CONCLUSION: These results showed that circ-MKLN1 contributed to the progression of PCO in vitro by increasing the CTGF expression via sponging miR-377-3p. Circ-MKLN1 might be important for improving the molecular target therapy in PCO.

AI-Model for Identifying Pathologic Myopia Based on Deep Learning Algorithms of Myopic Maculopathy Classification and "Plus" Lesion Detection in Fundus Images.

Background: Pathologic myopia (PM) associated with myopic maculopathy (MM) and "Plus" lesions is a major cause of irreversible visual impairment worldwide. Therefore, we aimed to develop a series of deep learning algorithms and artificial intelligence (AI)-models for automatic PM identification, MM classification, and "Plus" lesion detection based on retinal fundus images. Materials and Methods: Consecutive 37,659 retinal fundus images from 32,419 patients were collected. After excluding 5,649 ungradable images, a total dataset of 32,010 color retinal fundus images was manually graded for training and cross-validation according to the META-PM classification. We also retrospectively recruited 1,000 images from 732 patients from the three other hospitals in Zhejiang Province, serving as the external validation dataset. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, and quadratic-weighted kappa score were calculated to evaluate the classification algorithms. The precision, recall, and F1-score were calculated to evaluate the object detection algorithms. The performance of all the algorithms was compared with the experts' performance. To better understand the algorithms and clarify the direction of optimization, misclassification and visualization heatmap analyses were performed. Results: In five-fold cross-validation, algorithm I achieved robust performance, with accuracy = 97.36% (95% CI: 0.9697, 0.9775), AUC = 0.995 (95% CI: 0.9933, 0.9967), sensitivity = 93.92% (95% CI: 0.9333, 0.9451), and specificity = 98.19% (95% CI: 0.9787, 0.9852). The macro-AUC, accuracy, and quadratic-weighted kappa were 0.979, 96.74% (95% CI: 0.963, 0.9718), and 0.988 (95% CI: 0.986, 0.990) for algorithm II. Algorithm III achieved an accuracy of 0.9703 to 0.9941 for classifying the "Plus" lesions and an F1-score of 0.6855 to 0.8890 for detecting and localizing lesions. The performance metrics in external validation dataset were comparable to those of the experts and were slightly inferior to those of cross-validation. Conclusion: Our algorithms and AI-models were confirmed to achieve robust performance in real-world conditions. The application of our algorithms and AI-models has promise for facilitating clinical diagnosis and healthcare screening for PM on a large scale.

TRPML1 Inhibited Photoreceptor Apoptosis and Protected the Retina by Activation of Autophagy in Experimental Retinal Detachment.

OBJECTIVE: In this study, we used a rat model of retinal detachment (RD) to investigate the effects of transient receptor potential mucolipin 1 (TRPML1) on photoreceptor cells and the underlying mechanism. METHODS: An RD model was established by subretinal injection of sodium hyaluronate, and mucolipin synthetic agonist 1 (ML-SA1) and dimethyl sulphoxide were subretinally injected after RD induction. Retinal morphology was observed using haematoxylin-eosin staining, and the apoptosis of photoreceptor cells was detected by transmission electron microscopy. Reactive oxygen species (ROS) were examined with an ROS detection kit. The retinal expression levels of TRPML1, the autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), Beclin 1, and cleaved caspase 3 were detected by Western blotting. The Morris water maze was used to test vision-dependent behaviour. RESULTS: We found that retinal structure and the outer nuclear layer were improved and that the apoptosis of photoreceptor cells was reduced after ML-SA1 injection. The expression of ROS was reduced, and the loss of TRPML1 was inhibited after ML-SA1 treatment. The LC3-II to LC3-I ratio and Beclin 1 expression were enhanced, and cleaved caspase 3 expression was decreased after ML-SA1 treatment. Treatment with ML-SA1 also improved vision-dependent behaviour. CONCLUSIONS: Our findings suggest that ML-SA1 attenuates photoreceptor apoptosis and improves vision-dependent behaviour by activation of autophagy.

LncRNA KCNQ1OT1 knockdown inhibits viability, migration and epithelial-mesenchymal transition in human lens epithelial cells via miR-26a-5p/ITGAV/TGF-beta/Smad3 axis.

BACKGROUND: Long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) takes part in diabetic cataract progression. This research aims to analyze the function and mechanism of KCNQ1OT1 on viability, migration and epithelial-mesenchymal transition (EMT) in lens epithelial cells. METHODS: 20 diabetic cataract posterior lens capsule tissues and normal samples were collected. Lens epithelial cells (SRA01/04) were stimulated via high glucose (HG). The levels of KCNQ1OT1, miR-26a-5p, integrin αV (ITGAV), TGF-ß, Smad3 and phosphorylated (p)-Smad3 were measured via quantitative real-time polymerase chain reaction or Western blot. Cell viability, migration and EMT were analyzed via MTT, wound healing, transwell and Western blot assays. The target relationship between miR-26a-5p and KCNQ1OT1 or ITGAV was determined via luciferase reporter assay. RESULTS: KCNQ1OT1 was up-regulated and miR-26a-5p level was reduced in diabetic cataract tissues and HG-treated SRA01/04 cells. Silence of KCNQ1OT1 or miR-26a-5p up-regulation repressed cell viability, migration and EMT in SRA01/04 cells stimulated via HG. KCNQ1OT1 could target miR-26a-5p and controlled cell viability, migration and EMT via regulating miR-26a-5p. ITGAV was targeted via miR-26a-5p and positively regulated via KCNQ1OT1. ITGAV overexpression promoted cell viability, migration and EMT in HG-treated SRA01/04 cells, which were mitigated by KCNQ1OT1 silence. KCNQ1OT1 knockdown mitigated HG-induced the activation of TGF-ß/Smad3 signaling by regulating miR-26a-5p. CONCLUSION: KCNQ1OT1 knockdown represses cell viability, migration and EMT through miR-26a-5p/ITGAV/TGF-ß/Smad3 axis in SRA01/04 cells under HG condition, providing a new target for the treatment of diabetic cataract.

Dehaze of Cataractous Retinal Images Using an Unpaired Generative Adversarial Network.

Cataracts are the leading cause of visual impairment worldwide. Examination of the retina through cataracts using a fundus camera is challenging and error-prone due to degraded image quality. We sought to develop an algorithm to dehaze such images to support diagnosis by either ophthalmologists or computer-aided diagnosis systems. Based on the generative adversarial network (GAN) concept, we designed two neural networks: CataractSimGAN and CataractDehazeNet. CataractSimGAN was intended for the synthesis of cataract-like images through unpaired clear retinal images and cataract images. CataractDehazeNet was trained using pairs of synthesized cataract-like images and the corresponding clear images through supervised learning. With two networks trained independently, the number of hyper-parameters was reduced, leading to better performance. We collected 400 retinal images without cataracts and 400 hazy images from cataract patients as the training dataset. Fifty cataract images and the corresponding clear images from the same patients after surgery comprised the test dataset. The clear images after surgery were used for reference to evaluate the performance of our method. CataractDehazeNet was able to enhance the degraded image from cataract patients substantially and to visualize blood vessels and the optic disc, while actively suppressing the artifacts common in application of similar methods. Thus, we developed an algorithm to improve the quality of the retinal images acquired from cataract patients. We achieved high structure similarity and fidelity between processed images and images from the same patients after cataract surgery.

Retinal break associated with traumatic lens dislocation or subluxation requiring vitrectomy.

BACKGROUND: Both ectopia lentis and retinal injury are common results of blunt ocular trauma. Here, we investigated the incidence and characteristics of retinal breaks associated with ectopia lentis caused by blunt ocular trauma. METHODS: Patients who underwent pars plana vitrectomy to treat traumatic lens subluxation and dislocation were retrospectively reviewed. The incidence, characteristics, and outcomes of retinal breaks were analyzed. RESULTS: Forty-five eyes from 45 patients were included in the study. Seventeen eyes (37.7%) were complicated by retinal breaks or detachment, but only four (8.9%) were identified pre-operation. Our study revealed that retinal breaks were more frequently located at the superior (72.7%) and peripheral (81.8%) retina. All patients achieved anatomic recovery post-surgery. The eyes with and without retinal breaks did not differ significantly with respect to initial or final visual acuity. The final visual outcomes were independently and significantly associated with visual acuity at presentation (P = 0.001). CONCLUSIONS: Retinal breaks occurred in approximately one-third of patients with traumatic ectopia lentis and were difficult to observe pre-operation. Complete ophthalmic evaluation and timely intervention may help achieve favorable outcomes.

TRPV4 regulates migration and tube formation of human retinal capillary endothelial cells.

BACKGROUND: Ca2+ entry plays an important role in modulating endothelial cell migration and tube formation. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a Ca2+-permeable channel that is widely expressed in endothelial cells. It has been reported that TRPV4 is expressed in HRCECs and regulates Ca2+ entry. However, the function of TRPV4 in human retinal capillary endothelial cells (HRCECs) remains unknown. METHODS: In this study we used western blot and immunostaining assay to verify TRPV4 expression in HRCECs. And then we pretreated HRCECs with HC067047 and transfected with specific shRNA of TRPV4. The functional presence of TrpV4 was determined by using fluorescence, migration and tube formation assay in TrpV4 knockdown cells or control cells. RESULTS: Using western blot and immunostaining, we confirmed TRPV4 expression in HRCECs. Moreover, inhibition of TRPV4 using the specific inhibitor HC067047 and the knockdown of TRPV4 with shRNA significantly suppressed tube formation and migration by HRCECs. CONCLUSIONS: TRPV4 is essential for HRCEC migration and tube formation, and maybe a potential therapeutic target for retinal vascular diseases.

Altered Expression Profile of Circular RNAs in the Serum of Patients with Diabetic Retinopathy Revealed by Microarray.

PURPOSE: Diabetic retinopathy (DR) is the leading cause of blindness among working age adults. Circular RNAs (circRNAs) are a kind of noncoding RNAs that are involved in the development of some diseases. Here, we aimed to determine the possible role of circRNAs in the pathogenesis of DR by determining the expression profile of circRNAs in the serum of DR patients. METHODS: Nineteen subjects with type 2 diabetes mellitus with proliferative DR (T2DR), 15 subjects with type 2 diabetes mellitus without DR (T2DM), and 21 age-matched nondiabetic control subjects were included in the study. Expression profiles in the serum samples from 5 subjects of each group were studied by circular microarray and validated by quantitative real-time polymerase chain re- action (qRT-PCR) in another 40 subjects. Bioinformatic software was used to predict the microRNA response elements. RESULTS: Thirty circRNAs were significantly upregulated in the serum of T2DR patients compared with the serum from both T2DM and control patients. Further, the altered expression of 7 circRNAs (hsa_circRNA_063981, hsa_circRNA_ 404457, hsa_circRNA_100750, hsa_circRNA_406918, hsa_ circRNA_104387, hsa_circRNA_103410, and hsa_circRNA_ 100192) were verified by qRT-PCR. CONCLUSION: This study suggested a potential role of circRNAs in the pathogenesis of DR and provides novel molecular targets for clinical therapy.

Expression and role of specificity protein 1 in the sclera remodeling of experimental myopia in guinea pigs.

AIM: To study the expression of collagen I and transcription factor specificity protein 1 (Sp1), a transforming growth factor-ß1 (TGF-ß1) downstream target, and reveal the impact of the TGF-ß1-Sp1 signaling pathway on collagen remodeling in myopic sclera. METHODS: Seventy-five 1-week-old guinea pigs were randomly divided into normal control, form deprivation myopia (FDM), and self-control groups. FDM was induced for different times using coverage with translucent latex balloons and FDM recovery was performed for 1wk after 4wk treatment; then, changes in refractive power and axial length were measured. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera of guinea pigs with emmetropia and experimental myopia, and the relationship between collagen I and Sp1 levels was analyzed. RESULTS: In the FDM group, the refractive power was gradually changed (from 2.09±0.30 D at week 0 to -1.23±0.69 D, -4.17±0.59 D, -7.07±0.56 D, and -4.30±0.58 D at weeks 2, 4, 6, and 1wk after 4wk, respectively; P<0.05), indicating deepening of myopia. The axial length was increased (from 5.92±0.39 mm at week 0 to 6.62±0.36 mm, 7.30±0.34 mm, 7.99±0.32 mm, and 7.41±0.36 mm at weeks 2, 4, 6, and 1wk after 4wk; P<0.05). The mRNA and protein expression of Sp1 and collagen I in the sclera of the FDM group was lower than that of the control groups (P<0.05), and the reduction was eye-coverage time-dependent. Furthermore, correlation between Sp1 and collagen I down-regulation in the myopic sclera was observed. CONCLUSION: Our data indicate that transcription factor Sp1 may be involved in the regulation of type I collagen synthesis/degradation during myopic sclera remodeling, suggesting that TGF-ß1 signaling plays a role in the development and progression of myopia.

Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients.

AIM: To comprehensively analyze the risk factors of rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS: A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B-scan ultrasonography, and ultrasound biomicroscope (UBM). Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD). Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS: There were 52 eyes (19.62%) with CD. Pseudophakia was more commonly seen in RRDCD (21.15% vs 6.10%, P=0.002). Intraocular pressure (IOP) was lower (8.60±3.62 vs 12.96±3.55, P<0.001), best-corrected visual acuity was worse [3.00 (2.00 to 3.00) vs 1.92 (1.22 to 3.00), P=0.001], and refractive error was more myopic [-4 (-9 to -2) vs -2 (-6 to 0), P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment (P=0.007). In RRDCD, 34.62% of eyes presented with multiple holes (P=0.044) and 25.00% with macular holes (P=0.012), compared with 20.66% and 14.08% in RRD. High myopia (P=0.039), low IOP (P=0.017), and larger extent of retinal detachment (P<0.001) were significant and independent risk factors for developing CD. CONCLUSION: For CD in RRD, related factors include BCVA, IOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low IOP are significant and independent risk factors.

Effects of scleral encircling surgery on vitreous cavity length and diopter.

AIM: To observe the changes of vitreous cavity length and diopter after scleral encircling (SE) produce. METHODS: This prospective study included 68 eyes of 68 non-consecutive patients with macula-off retinal detachment who were operated by SE surgery. The corneal refractive power, ocular axial length and diopter were measured by keratometer, A-mode ultrasonic meter and computed dioptometer. RESULTS: There was no significant difference in corneal refractive power among preoperative and postoperative 1, 3 and 6 mo (0.57±0.54 D at pre-surgery;0.72±0.26 D at 1mo; 0.71±0.34 D at 3mo; 0.69±0.31 D at 6mo; all P>0.05 ). Axial lengths were obviously lengthened, especially in vitreous cavity length (17.87±3.09 mm, 19.69±3.12 mm, 18.97±3.56 mm, 18.76±3.47 mm, 18.68±3.42 mm at pre-surgery, 1wk, 1, 3 and 6mo postoperatively, P <0.05) and diopter also increased at beginning and then recovered gradually. After 1 and 3 mo, axial length (vitreous cavity length) and myopia were more and in higher degree than before surgery. CONCLUSION: The change of postoperative vitreous cavity length is the main factor that results in the changes of axial length and then makes the change of diopter.

Silencing Matrix Metalloproteinases 9 and 2 Inhibits Human Retinal Microvascular Endothelial Cell Invasion and Migration.

PURPOSE: Proliferative retinal angiogenesis may severely impair the retina. Previous studies have indicated that matrix metalloproteinase (MMP)-2 and MMP-9 play important roles in the process of retinal angiogenesis. In this study, we suppressed MMP-2 and MMP-9 expression with RNA interference (RNAi) and then observed the inhibitory effects on the invasion and migration of human retinal microvascular endothelial cells (HRMECs). METHODS: Small interfering RNAs against MMP-2 mRNA and MMP-9 mRNA were synthesized. After transfection, the MMP-2 and MMP-9 expression in HRMECs was examined by real-time polymerase chain reaction and Western blot analysis. Cell migration and invasion were measured with a migration assay and a scratch wound assay, respectively. RESULTS: RNAi against MMP-2 and MMP-9 successfully inhibited the mRNA and protein expression of MMP-2 and MMP-9 in HRMECs. MMP-2 and MMP-9 knockdown could inhibit the invasion and migration of HRMECs. CONCLUSIONS: These findings suggest that the RNAi approach towards MMP-2 and MMP-9 may be a potentially effective therapeutic method for the treatment of proliferative retinal angiogenesis.

Activation of autophagy in photoreceptor necroptosis after experimental retinal detachment.

AIM: To investigate whether photoreceptor necroptosis induced by z-VAD-FMK (pan caspase inhibitor) was involved the activation of autophagy and whether Necrostatin-1, a specific necroptosis inhibitor, could inhibit this induction of autophagy after experimental retinal detachment. METHODS: Experimental retinal detachment models were created in Sprague-Dawley rats by subretinal injection of sodium hyaluronate and subretinal injections of z-VAD-FMK, vehicle or z-VAD-FMK plus Necrostatin-1. Three days after retinal detachment, morphologic changes were observed by transmission electron microscopy. In other animals, retinas were subjected to immunoprecipitation and Western Blotting, then probed with anti-RIP1, phosphoserine, LC-3II or caspase 8 antibody. RESULTS: It was proved by immunoprecipitation and western blotting, that photoreceptor necroptosis was mediated by caspase-8 inhibition and receptor interacting protein kinase (RIP1) phosphorylation activation. Transmission electron microscope and western blotting results indicated that photoreceptor necroptosis was involved the LC-3II and autophagosomes induction. We also discovered Necrostatin-1 could inhibit RIP1 phosphorylation and LC-3II induction. CONCLUSION: These data firstly indicate photoreceptor necroptosis is associated with the activation of autophagy. Necrostatin-1 protects photoreceptors from necroptosis and autophagy by down-regulation of RIP1 phosphorylation and LC-3II.

[Supracapsular implantation with optic capture of posterior chamber intraocular lens in aphakic school-age children after traumatic cataract].

OBJECTIVE: To assess the clinical effects of supracapsular implantation with optic capture of the posterior chamber intraocular lens in school-age children with traumatic cataract. METHOD: It was a retrospective case series study. Thirteen cases (13 eyes) received posterior curvilinear capsulorhexis with optic capture of the posterior chamber intraocular lens. Pre- and post-operative visual acuities were recorded. Intra-o and post-operative complications were observed. The follow-up period ranged from 6 to 42 months. RESULTS: Implantation of optic capture of the posterior chamber intraocular lens was successfully performed in 13 eyes. The best-corrected-visual acuity ranged from 0.2 to 1.0. No optic axis opaque was found in 10 eyes with optic capture. The major complications of optic capture were lenticular precipitates and posterior synechia of the iris. Intraocular dislocation was found in one case two weeks after the operation. CONCLUSIONS: Supracapsular implantation with optic capture of the posterior chamber intraocular lens is safe and effective for the treatment of traumatic cataract in school-age children.

[Effects of blocking activation of IGF-1-Stat3 signaling pathway in guinea pig sclera fibroblast by AG490 on expression of MMP-2 and Integrinß(1)].

OBJECTIVE: To explore the effect of Blocking activation of IGF-1-Stat3 signaling pathway in guinea pig sclera fibroblast (GSFs) by AG490 on expressions of MMP-2, Integrinß(1). METHODS: Cultured GSFs were divided into four groups: group A(control group: only DMEM without IGF-1), group B (only IGF-1 group), group C(IGF-1 + PBS group), group D (IGF-1 + 25 µmol/L AG490 group). The expressions of Stat3, p-Stat3, MMP-2, Integrinß(1) protein induced by IGF-1 and inhibited by AG490 in GSFs were detected by Western blot. The levels of Stat3, MMP-2 and Integrinß(1)mRNA were detected by RT-PCR. RESULTS: Compared with Groups A and D, Stat3, p-Stat3, MMP-2 protein expression in groups B and C were expressed at higher level (t(pr) = -32.324, -26.284, -32.876, -26.345, -68.668, -58.724, -187.481, -58.842, -110.264, -120.256, -121.345, -120.286; t(mRNA) = -31.554, -31.178, -31.286, -31.198, -12.076, -14.969, -11.896, -14.546, P < 0.05), but the expression levels were not obviously different between groups B and C (t(p) = -32.720, -32.816, -68.668, -187.481, -110.264, -121.345; t(mRNA) = -0.692, -0.579, P > 0.05), which were similar to mRNA level. The Integrinß(1) protein and mRNA were expressed in groups A, B, C and D but no significant difference among them respectively (F(pr) = 0.214;F(mRNA) = 0.045, P > 0.05). CONCLUSIONS: Activation of Stat3 signaling pathway may be involved in up-modulating the expression of MMP-2 in GSFs, and not affect the Integrinß(1) protein and mRNA changes. The results reveal that Stat3 signaling transduction pathway may play a critical role in sclera remodeling by means of modulating MMP-2 expression.

Posterior scleral reinforcement in the treatment of macular retinoschisis in highly myopic patients.

The objective of this study was to evaluate the clinical curative effect of posterior scleral reinforcement for macular retinoschisis in highly myopic patients. Twenty-four highly myopic eyes with macular retinoschisis were treated with posterior scleral reinforcement surgery from September 2005 to March 2007 in our hospital. Visual field, best corrected vision acuity (BCVA), refractive error, optical coherence tomography and A/B Scan ultrasound graphy results were retrospectively analysed. The central visual field in 18 eyes was improved after surgery; optical coherence tomography showed complete resolution of the myopic foveoschisis in 20 (83.33%) of the 24 eyes after surgery. The postoperative BCVA was improved by 0.1 or more in 18 eyes (75%), and remained within 0.1 of the preoperative BCVA in five eyes (20.83%) at the end of follow-up. Compared with the preoperative data of 23 eyes, the final magnitude of myopia after surgery was significantly decreased (t = 3.527, P = 0.002). In conclusion, this procedure can effectively treat highly myopic patients with macular retinoschisis without macular hole or retinal detachment, and might be better for maintaining central vision and preventing the occurrence of complications.

Protective effect of perindopril on diabetic retinopathy is associated with decreased vascular endothelial growth factor-to-pigment epithelium-derived factor ratio: involvement of a mitochondria-reactive oxygen species pathway.

OBJECTIVE: This study aimed to verify whether the decreased vascular endothelial growth factor (VEGF)-to-pigment epithelium-derived factor (PEDF) ratio can serve as an indicator for the protective effect of angiotensin-converting enzyme inhibitors (ACEIs) on diabetic retinopathy (DR) and to investigate the role of mitochondrial reactive oxygen species (ROS) in the downregulated VEGF-to-PEDF ratio. RESEARCH DESIGN AND METHODS: Diabetic rats and control animals were randomly assigned to receive perindopril or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without perindopril. VEGF, PEDF, PPARgamma, and uncoupling protein-2 (UCP-2) in the rat retinas or BREC extracts were examined by Western blotting and real-time RT-PCR. The levels of VEGF and PEDF in cell culture media were examined by ELISA. Mitochondrial membrane potential (Deltapsim) and ROS production were assayed using JC-1 or CM-H2DCFDA. RESULTS: The VEGF-to-PEDF ratio was increased in the retina of diabetic rats; perindopril lowered the increased VEGF-to-PEDF ratio in diabetic rats and ameliorated the retinal damage. In BRECs, perindopril lowered the hyperglycemia-induced elevation of VEGF-to-PEDF ratio by reducing mitochondrial ROS. We found the decreased ROS production was a result of perindopril-induced upregulation of PPARgamma and UCP-2 expression and the subsequent decrease of Deltapsim. CONCLUSIONS: It is concluded that the protective effect of ACEI on DR is associated with a decreased VEGF-to-PEDF ratio, which involves the mitochondria-ROS pathway through PPARgamma-mediated changes of UCP-2. This study paves a way for future application of ACEI in treatment of DR.