Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma.

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- ß signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.

[Characterization of Microplastic Surface Bacterial Community Structure and Prediction of Ecological Risk in Poyang Lake, China].

In recent years, the environmental pollution of microplastics in Poyang Lake has received increasing attention. Baisha Lake of Poyang Lake was selected as the study area, and samples of water and sediments of Baisha Lake and the microplastics therein were collected, and the polymer types of microplastics were identified as polyethylene (PE), polyester (PET), polypropylene (PP), and polystyrene (PS) using Fourier infrared spectroscopy. We also analyzed the structural composition of bacterial communities in water, in sediments, and on microplastic surfaces using 16S high-throughput sequencing. The species richness and diversity of bacteria on the microplastic surfaces were lower than those in the surrounding water and sediments. The results of NMDS analysis showed that the bacterial community structures on the microplastic surfaces differed greatly from those in the surrounding sediments and water. The bacterial community composition in water and sediment differed from that on the microplastic surfaces, and the dominant bacterial phyla on the microplastic surfaces were Proteobacteria and Bacteroidota, and their relative abundance on the microplastic surfaces was higher than that in sediment. The relative abundance of Proteobacteria was higher than that in water. The relative abundances of Bacteroidota and Actinobacteriota were significantly lower than that of water. Massilia and Pseudomonas were the dominant genera on the microplastic surfaces, and their relative abundances were significantly higher than those in the surrounding water and sediments. BugBase phenotype prediction revealed that the relative abundance of contains mobile elements, biofilm formation, potential pathogenicity, and stress tolerance phenotypes of microplastic bacterial communities were significantly higher than those of the surrounding water and sediments. The results revealed that microplastics may have contributed to the spread of harmful bacteria, including pathogenic bacteria, and increased the potential pathogenicity of bacterial communities. Additionally, microplastic surface bacterial communities had higher phenotypes of mobile gene element content. Revealing the potential harm of microplastic pollution to wetland ecology at the micro level may provide a scientific reference for maintaining the ecological stability of wetlands.

Expression of ATP-Binding Cassette Transporter A1 (ABCA1) in Eyelid Tissues and Meibomian Gland Epithelial Cells.

Purpose: To validate the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression and distribution in human eyelid tissues and meibomian gland epithelial cells. Methods: Meibomian gland tissues from human eyelids were isolated by collagenase A digestion and cultured in defined keratinocyte serum-free medium (DKSFM). Infrared imaging was used to analyze the general morphology of meibomian glands. Hematoxylin and eosin (H&E) staining and Oil Red O staining were used to observe the morphological structure and lipid secretion in the human meibomian gland tissues. Quantitative real-time polymerase chain reaction, western blotting, and immunostaining were used to detect the mRNA and protein expression and cytolocalization of ABCA1 in the meibomian gland tissues and cultured cells. Results: The degree of loss of human meibomian gland tissue was related to age. Meibomian gland lipid metabolism was also associated with age. Additionally, human meibomian gland tissues express ABCA1 mRNA and protein; glandular epithelial cells express more ABCA1 mRNA and protein than acinar cells, and their expression in acinar cells decreases with differentiation. Furthermore, the expression of ABCA1 was downregulated in abnormal meibomian gland tissues. ABCA1 was mainly localized on the cell membrane in primary human meibomian gland epithelial cells (pHMGECs), whereas it was localized in the cytoplasm of immortalized human meibomian gland epithelial cells (iHMGECs). The mRNA and protein levels of ABCA1 in pHMGECs were higher than those in iHMGECs. Conclusions: Meibomian gland tissues of the human eyelid degenerate with age. ABCA1 expression in acinar cells decreases after differentiation and plays an important role in meibomian gland metabolism.

Microcatheter-Assisted Circumferential Trabeculotomy After Failed Glaucoma Surgeries in Childhood Glaucoma.

PURPOSE: To evaluate the outcomes of microcatheter-assisted trabeculotomy (MAT) in childhood glaucoma (primary congenital glaucoma [PCG], juvenile open-angle glaucoma [JOAG], and secondary childhood glaucoma [SCG]) after failed glaucoma surgery. DESIGN: Retrospective interventional case series. METHODS: Patients with childhood glaucoma who underwent MAT after failed glaucoma surgery with at least 12 months of follow-up were evaluated. Pre- and postoperative intraocular pressure (IOP) and the number of glaucoma medications were recorded and compared. Success was defined as an IOP ≤21 mm Hg with or without glaucoma medication. Analysis of variance was used to compare the glaucoma subgroups. RESULTS: Forty-five eyes (42 patients) with a median follow-up period of 19 months were included. The median age at the time of MAT was 10 (range, 0.8-33) years. The mean number of previous surgeries was 1.3 ± 0.5. The IOP had significantly reduced from baseline in all PCG, JOAG, and SCG patients (27.9 ± 4.5 vs 16.3 ± 8.0 mm Hg, P = .001; and 30.8 ± 9.4 vs 13.5 ± 3.0 mm Hg, P < .001; and 31.5 ± 7.1 vs 16.5 ± 5.3 mm Hg, P = .001, respectively). Fewer glaucoma medications were needed after MAT in all 3 groups (each P < .001). At the last visit, the total success rates in PCG, JOAG, and SCG were 93.8%, 100%, and 88.9%, respectively. No severe complications were observed. CONCLUSION: MAT can effectively manage PCG, JOAG, and SCG after failed surgeries, providing successful outcomes and no serious complications. Following failed glaucoma surgeries, MAT may offer these patients with childhood glaucoma an excellent opportunity to achieve IOP control.

Deciphering Adult Neural Stem Cells with Single-Cell Sequencing.

Adult neural stem cells (NSCs) are restricted to the two neurogenic regions of the mammalian brain, where they self-renew and generate progenies of multiple lineages, including neurons, astrocytes, and oligodendrocytes. Single-cell RNA sequencing technology, which reconstructs high-resolution transcriptional landscapes, provides valuable insights into cellular heterogeneity and developmental dynamics. In this review, we overviewed recent progress in the single-cell analyses of both conventional and unconventional NSCs. We discussed the heterogeneity among the stem cell pool and characterized the transcriptional alterations in aging and brain tumors. A comprehensive understanding of NSCs in physiological and pathological settings will provide insights for the rejuvenation of the aged brain and restoration of normal brain function in multiple neurological disorders.

Retinal nerve fibre layer thickness measured with SD-OCT in a population-based study: the Handan Eye Study.

PURPOSE: To examine the normative profile of retinal nerve fibre layer (RNFL) thickness and ocular parameters based on spectral-domain optical coherence tomography (SD-OCT) and its associations with related parameters among the Chinese population. METHODS: This population-based cohort Handan Eye Study (HES) recruited participants aged≥30 years. All subjects underwent a standardised ophthalmic examination. Peripapillary RNFL thickness was obtained using SD-OCT. Mixed linear models were adopted to evaluate the correlation of RNFL thickness with ocular parameters as well as systemic factors. R V.3.6.1 software was used for statistical analysis. RESULTS: 3509 subjects (7024 eyes) with the average age of 55.54±10.37 were collected in this analysis. Overall mean RNFL thickness measured was 113.46±10.90 µm, and the thickest quadrant of parapapillary RNFL was the inferior quadrant, followed by the superior quadrant, the nasal quadrant and the temporal quadrant. In the multivariate linear regression model, thinner RNFL thickness was remarkable association with male (p<0.001), older age (p<0.001), increased body mass index (>30, p=0.018), absence of diabetes (p=0.009), history of cataract surgery (p=0.001), higher intraocular pressure (p=0.007), lower spherical equivalent (p<0.001) and increased axial length (p=0.048). CONCLUSIONS: In non-glaucoma individuals, this difference of RNFL thickness in Chinese population should be noted in making disease diagnoses. Meanwhile, multiple ocular and systemic factors are closely related to the thickness of RNFL. Our findings further emphasise the need to demonstrate ethnic differences in RNFL thickness and the specificity of associated ocular and systemic factors, as well as to develop better normative databases worldwide. TRIAL REGISTRATION NUMBER: HES was registered in Chinese Clinical Trial Registry website, and the registry number was ChiCTR-EOC-17013214.

Use of ultrasound biomicroscopy to predict the outcome of anterior segment reconstruction in congenital fibrovascular pupillary membrane with secondary glaucoma.

AIMS: To evaluate the efficacy and safety of anterior segment reconstruction (ASR) in congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG) basing ultrasound biomicroscopy (UBM) classification. METHODS: This ambispective cohort study enrolled patients with CFPMSG who underwent ASR between January 2014 and September 2020. Comprehensive ophthalmic examinations and UBM were performed before surgery and postoperatively. The patients were classified into three types according to the UBM configurations. Anterior chamber recovery (ACR) was defined as deepening in anterior chamber (≥1.5 mm all through final follow-up (FFU), while success following ASR was defined as ACR and intraocular pressure (IOP)≤21 mm Hg. RESULTS: 25 eyes of 25 patients underwent ASR (average age at operation 5.8±5.0 months, 48% girls) with FFU 15.8±16.9 months. Enrolled subjects were classified into type Ⅰ (11 eyes), type Ⅱ (11 eyes) and type Ⅲ (3 eyes). After ASR, 23 eyes (92%) achieved ACR, and the mean ACD increased in all groups (p=0.006, <0.001 and 0.003, respectively). Eyes with types Ⅰ and Ⅱ demonstrated a reduction of IOP (p=0.009 and 0.002, respectively). ASR success rate was highest in type Ⅰ (72.9%) compared with types Ⅱ and Ⅲ (18.2% and 0%, respectively; p=0.011). ASR led to decreased number of antiglaucoma medications for type Ⅰ CFPMSG at FFU (p=0.016). No vision-threatening postoperative complications occurred. CONCLUSIONS: ASR for CFPMSG results in increased ACD and improvement in IOP. Postoperative IOP control was best in type Ⅰ CFPMSG but not as effective in types Ⅱ and Ⅲ. UBM-based classification helps to predict the surgical outcome of ASR in CFPMSG.

Effect of Combined Surgery in Patients with Complex Nanophthalmos.

(1) Background: To evaluate the efficacy and safety of combined surgery (limited pars plana vitrectomy, anterior-chamber stabilized phacoemulsification, IOL implantation and posterior capsulotomy, LPPV + ACSP + IOL + PC) in complex nanophthalmos. (2) Methods: Patients with complex nanophthalmos were recruited to undergo LPPV + ACSP + IOL + PC from January 2017 to February 2021. Preoperative and post-operative intraocular pressure (IOP), best corrected visual acuity (BCVA), anterior chamber depth (ACD), and number of glaucoma medications were compared using the paired t-test or Wilcoxon signed rank sum tests. Surgical success rate was evaluated. Surgery-associated complications were documented. (3) Results: Forty-five eyes of 37 patients with complex nanophthalmos were enrolled. The mean follow-up period was 21.7 ± 10.6 months after surgery. Mean IOP decreased from 32.7 ± 8.7 mmHg before surgery to 16.9 ± 4.5 mmHg (p < 0.001) at the final follow-up visit, mean logMAR BCVA improved from 1.28 ± 0.64 to 0.96 ± 0.44 (p < 0.001), mean ACD significantly increased from 1.14 ± 0.51 mm to 3.07 ± 0.66 mm (p < 0.001), and the median number of glaucoma medications dropped from 3 (1, 4) to 2 (0, 4) (p < 0.001). The success rate was 88.9% (40 eyes) at the final follow-up visit. Two eyes had localized choroidal detachments which resolved with medical treatment. (4) Conclusions: LPPV + ACSP + IOL + PC is a safe and effective surgical procedure, which can decrease IOP, improve BCVA, deepen the anterior chamber, and reduce the number of glaucoma medications in patients with complex nanophthalmos. It can be considered as one of the first treatment in nanophthalmic eyes with complex conditions.

Lens nucleus dislocation in hypermature cataract: Case report and literature review.

INTRODUCTION: Hypermature cataract is a form of late-stage cataract progression that can lead to a variety of complications. Spontaneous capsular rupture with lens nucleus displacement in hypermature cataracts has rarely been reported. We describe 2 cases of spontaneous dislocation of the lens nucleus in a hypermature cataract and perform a review of the literature on this complication. PATIENT CONCERNS: We report 2 rural men aged 50 and 76 years with deteriorating vision. DIAGNOSIS: The final diagnosis was senile hypermature cataract with dislocation of the lens nucleus in both patients and secondary glaucoma for the second patient. INTERVENTIONS AND OUTCOMES: During admission, both patients complained of deteriorating vision. Slit-lamp examination showed lens nucleus dislocation into the anterior chamber. The 50-year-old patient exhibited a residual lens capsule and a turbid cortex, with a normal anterior chamber and intraocular pressure. The 76-year-old patient presented a shrunken and ruptured capsule and no cortex in the pupillary area, mild inflammation in the anterior chamber, and high intraocular pressure. Both patients underwent intracapsular cataract extraction combined with anterior vitrectomy and achieved good postoperative recovery. CONCLUSION: Lens nucleus dislocation in hypermature cataracts can be seen in clinical practice, particularly in underdeveloped areas. Early recognition and surgery can improve vision.

TNF-α stimulation enhances the neuroprotective effects of gingival MSCs derived exosomes in retinal ischemia-reperfusion injury via the MEG3/miR-21a-5p axis.

Retinal ischemia-reperfusion injury (IRI) is one of the main pathogenic mechanisms of glaucoma, which are largely unknown, including neuroinflammation and neuronal death in the pathological process. In our previous studies, mesenchymal stem cells (MSCs) have been reported to play anti-inflammatory and neuroprotective roles. Additionally, conditioned culture medium (CM) of MSCs stimulated by TNF-α have achieved better antiallergic effects in an experimental allergic conjunctivitis mouse model. However, there is an urgent need for cell-free therapy approaches, like exosomes, to reduce the side effects of autoimmunity. The present study aimed to elucidate the pathways involving TNF-α-stimulated gingival MSC (GMSC)-exosomes (TG-exos), in modulating inflammatory microglia and alleviating apoptosis. In this study, exosomes from the CM of GMSCs were isolated by ultracentrifugation and were injected into the vitreous of mice. The results showed that intraocular injection of TG-exos into mice with IRI notably reduced inflammation and cell loss than that with G-exos (GMSC-exosomes). Similar results were observed in vitro. Additionally, with the microRNA (miR) arrays, it was found that miR-21-5p acted as a crucial factor in TG-exos for neuroprotection and anti-inflammation. Following target prediction and dual-luciferase assay suggested that miR-21-5p played a role by combining with programmed cell death 4 (PDCD4), which was regulated by the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) as a competing endogenous RNA (ceRNA). This study demonstrates a new therapeutic pathway for neuroprotection against IRI by delivering miR-21-5p-enriched exosomes through MEG3/miR-21-5p/PDCD4 axis and paves the way for the establishment of a cell-free therapeutic approach for glaucoma.

Characteristic Assessment of Angiographies at Different Depths with AS-OCTA: Implication for Functions of Post-Trabeculectomy Filtering Bleb.

This study aimed to analyze the quantitative vascular biomarkers of filtering bleb function at different depths using anterior segment optical coherence tomography angiography (AS-OCTA). This cross-sectional study is registered on Clinicaltrails.gov (NCT04515017). Forty-six eyes with primary open-angle glaucoma that had undergone trabeculectomy with mitomycin-C for more than six months were included. Vessel density (VD) and vessel diameter index (VDI) in the superficial layer (SL), Tenon's layer (TL), and deep layer (DL) of the bleb were obtained. The VD and VDI were higher in the failure group (both p = 0.000). Significant correlations were found between the SL, TL, DL's VDI, and IOP in the success group (p = 0.013, 0.016, 0.031, respectively). The VD of the TL and DL were related to IOP in the failure group (p = 0.012, 0.009). Tenon's VD (TVD) and Tenon's VDI (TVDI) correlated with IOP adjusting for TVD, TVDI, and the Indiana Bleb Appearance Grading Scale (IBAGS) (p = 0.009, 0.043) or Kenfeld grading system (KGS) (p = 0.011, 0.016). The area under curve (AUC) of the TVD, TVDI, IBAGS, and KGS to predict surgery failure were 0.960, 0.925, 0.770, and 0.850. AS-OCTA realized the quantitative evaluation of vessels, especially the invisible vascularity beneath the conjunctiva. TVD and TVDI as detected by AS-OCTA better reflected bleb function than conventional grading systems.

Suppression of TGF-ß1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells.

The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregulated by dexamethasone. Continuous passage of these cells on 2D Matrigel resulted in a gradual loss of expression of these markers. However, such a loss was restored by seeding cells in 3D Matrigel where expression of TM markers was further upregulated upon continuous passage. In contrast, TM cells seeded on fibronectin, collagen I/IV, or laminin lost expression of these markers and turned into myofibroblasts with expression of αSMA, which were dose-dependently upregulated by TGF-ß1/TGF-ß2. TM cells in 3D Matrigel also expressed TGF-ß1/TGF-ß3 despite challenge of TGF-ß1. The maintenance of TM phenotype by 3D Matrigel was linked to inhibition of canonical TGF-ß signaling and activation of pFAK-pSrc-pP190RhoGAP-P120RasGAP signaling. These findings indicate that basement membrane matrix with low rigidity plays an active role in maintaining TM phenotype in the presence of TGF-ß1 and shed light on its physiological role. Furthermore, abnormal matrices may perpetuate the pathological TM phenotype when the level of TGF-ß2 is elevated in glaucoma patients.

TET-dependent GDF7 hypomethylation impairs aqueous humor outflow and serves as a potential therapeutic target in glaucoma.

Glaucoma is the leading cause of irreversible vision loss, affecting more than 70 million individuals worldwide. Circulatory disturbances of aqueous humor (AH) have long been central pathological contributors to glaucomatous lesions. Thus, targeting the AH outflow is a promising approach to treat glaucoma. However, the epigenetic mechanisms initiating AH outflow disorders and the targeted treatments remain to be developed. Studying glaucoma patients, we identified GDF7 (growth differentiation factor 7) hypomethylation as a crucial event in the onset of AH outflow disorders. Regarding the underlying mechanism, the hypomethylated GDF7 promoter was responsible for the increased GDF7 production and secretion in primary open-angle glaucoma (POAG). Excessive GDF7 protein promoted trabecular meshwork (TM) fibrosis through bone morphogenetic protein receptor type 2 (BMPR2)/Smad signaling and upregulated pro-fibrotic genes, α-smooth muscle actin (α-SMA) and fibronectin (FN). GDF7 protein expression formed a positive feedback loop in glaucomatous TM (GTM). This positive feedback loop was dependent on the activated TET (ten-eleven translocation) enzyme, which kept the GDF7 promoter region hypomethylated. The phenotypic transition in TM fortified the AH outflow resistance, thus elevating the intraocular pressure (IOP) and attenuating the nerve fiber layer. This methylation-dependent mechanism is also confirmed by a machine-learning model in silico with a specificity of 84.38% and a sensitivity of 89.38%. In rhesus monkeys, we developed GDF7 neutralization therapy to inhibit TM fibrosis and consequent AH outflow resistance that contributes to glaucoma. The neutralization therapy achieved high-efficiency control of the IOP (from 21.3 ± 0.3 to 17.6 ± 0.2 mmHg), a three-fold improvement in the outflow facility (from 0.1 to 0.3 µL/min · mmHg), and protection of nerve fibers. This study provides new insights into the epigenetic mechanism of glaucoma and proposes an innovative GDF7 neutralization therapy as a promising intervention.

HC-HA/PTX3 from amniotic membrane reverts senescent limbal niche cells to Pax6+ neural crest progenitors to support limbal epithelial progenitors.

Quiescence and self-renewal of human corneal epithelial progenitor/stem cells (LEPC) are regulated by the limbal niche, presumably through close interaction with limbal (stromal) niche cells (LNC). Paired box homeotic gene 6 (Pax6), a conserved transcription factor essential for eye development, is essential for proper differentiation of limbal and corneal epithelial stem cells. Pax6 haploinsufficiency causes limbal stem cell deficiency, which leads to subsequent corneal blindness. We previously reported that serial passage of nuclear Pax6+ LNC resulted in the gradual loss of nuclear Pax6+ and neural crest progenitor status, the latter of which was reverted upon recovery of Pax6. These findings suggest Pax6 plays a pivotal role in supporting the self-renewal of LEPC in limbal niche. Herein, we show that HC-HA/PTX3, a unique matrix purified from amniotic membrane (AM) and consists of heavy chain 1of inter-α-trypsin inhibitor covalently linked to hyaluronic acid and complexed with pentraxin 3, is capable of reverting senescent LNC to nuclear Pax6+ neural crest progenitors that support self-renewal of LEPC. Such reversion is causally linked to early cell aggregation mediated by activation of C-X-C chemokine receptor type 4 (CXCR4)-mediated signaling followed by activation of bone morphogenetic protein (BMP) signaling. Furthermore, CXCR4-mediated signaling, but not BMP signaling, controls recovery of the nuclear Pax6+ neural crest progenitors. These findings not only explain why AM helps in vivo and ex vivo expansion of human LEPC, but they also illuminate the potential role of HC-HA/PTX3 as a surrogate matrix niche that complements stem cell-based therapies in regenerative medicine.

COX-2 Signaling in the Tumor Microenvironment.

Tumorigenesis is a multistep, complicated process, and many studies have been completed over the last few decades to elucidate this process. Increasingly, many studies have shifted focus toward the critical role of the tumor microenvironment (TME), which consists of cellular players, cell-cell communications, and extracellular matrix (ECM). In the TME, cyclooxygenase-2 (COX-2) has been found to be a key molecule mediating the microenvironment changes. COX-2 is an inducible form of the enzyme that converts arachidonic acid into the signal transduction molecules (thromboxanes and prostaglandins). COX-2 is frequently expressed in many types of cancers and has been closely linked to its occurrence, progression, and prognosis. For example, COX-2 has been shown to (1) regulate tumor cell growth, (2) promote tissue invasion and metastasis, (3) inhibit apoptosis, (4) suppress antitumor immunity, and (5) promote sustainable angiogenesis. In this chapter, we summarize recent advances of studies that have evaluated COX-2 signaling in TME.

Effect of intraocular lens implantation on visual field in glaucoma and comorbid cataracts.

AIM: To investigate the effects of intraocular lens (IOL) implantation on visual field (VF) in patients with glaucoma and comorbid cataracts (G&C) with different disease severities. METHODS: Totally 56 eyes of 50 patients with primary G&C were included. All patients were divided into three groups based on the severity of the VF defect: the mild, moderate, and severe stage. Phacoemulsification was performed for cataract removal combined with IOL implantation. Visual acuity (VA) and VF tests were performed for all enrolled patients, up to 3mo after surgery. Changes in VF threshold and global VF index in various groups were also recorded before and after surgery. The mean light sensitivity (MS) values and the changes following surgery (DMS) were compared between the three groups. Advanced Glaucoma Intervention Study (AGIS) scoring was analyzed on all VF results for analysis of changes in VF before and after surgery. RESULTS: Following surgery, the MS values of the three groups of G&C increased significantly, while the AGIS scores decreased statistically in all groups. The DMS values for the three zones in moderate and severe stage but not mild stage were statistically different between zones. The DMS value was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.05). The DMS was significantly higher in zone I than that in zone III in moderate stage patients (zone I>zone II>zone III; P<0.01), while the DMS values in the severe stage patients was significantly higher in zone I than those in zone II and III (zone I>zone II>zone III; P<0.01). CONCLUSION: The mean VF sensitivity of glaucoma patients increased significantly after cataract removal and IOL implantation. Variations in the severity and distribution of characteristics of VF defects result in differences in postoperative VF improvements after cataract surgery. The magnitude of increase in VF sensitivity is associated with VF defect characteristic in glaucoma.

The Role of Cyclooxygenase-2 in Colorectal Cancer.

Colorectal cancer is the third common cancer in this world, accounting for more than 1 million cases each year. However, detailed etiology and mechanism of colorectal cancer have not been fully understood. For example, cyclooxygenase-2 (COX-2) and its product prostaglandin E2 (PGE2) have been closely linked to its occurrence, progression and prognosis. However, the mechanisms on how COX-2 and PGE2-mediate the pathogenesis of colorectal cancer are obscure. In this review, we have summarized recent advances in studies of pathogenesis and control in colorectal cancer to assist further advances in the research for the cure of the cancer. In addition, the knowledge gained may also guide the audiences for reduction of the risk and control of this deadly disease.

The in vitro anti-fibrotic effect of Pirfenidone on human pterygium fibroblasts is associated with down-regulation of autocrine TGF-ß and MMP-1.

We aimed to investigate the in vitro effect of pirfenidone (PFD) on proliferation, migration and collagen contraction of human pterygium fibroblasts (HPFs). HPFs were obtained from tissue explants during pterygium surgery. After treatment with pirfenidone, the HPFs proliferation was measured by MTT, cell cycle progression measured by flow cytometry, cell migration measured by the scratch assay, and cell contractility evaluated in fibroblast-populated collagen gels. The expression of TGF-ß1, TGF-ß2, MMP-1 and TIMP-1 were also determined with quantitative PCR, western blot and immunofluorescence staining. Results showed pirfenidone markedly inhibited HPFs proliferation with an IC50 of approximately 0.2 mg/ml. After treatment with 0.2 mg/ml pirfenidone for 24 hours, HPFs were at G0/G1 cell cycle arrest, with significantly reduced cell migration capability and collagen contraction, decreased mRNA and protein expressions of TGF-ß1, TGF-ß2 and MMP-1, and no alterations of TIMP-1 expression. Thus, we have concluded that pirfenidone at 0.2 mg/ml inhibits proliferation, migration, and collagen contraction of HPFs, which is associated with decreased expression of TGF-ß and MMP-1, and pirfenidone might represent a potentially therapeutic agent to prevent the recurrence of pterygium after surgery.

Differential Gene Expression between Limbal Niche Progenitors and Bone Marrow Derived Mesenchymal Stem Cells.

Purpose: To compare the difference in gene expression between human limbal niche cells (LNC) and bone marrow derived mesenchymal stem cells (BMMSC). Methods: LNC were isolated by collagenase and expanded in modified embryonic stem cell medium (MESCM) on a Matrigel coated plastic plate. Cell diameters were measured with Image J software. Relative gene expression levels between LNC and BMMSC were compared using Affymetrix Human Primer View Gene Expression Array. A subset of differentially expressed genes was verified by RT-qPCR. The protein level of LAMA1 and COL4A1 was confirmed by Western blot and immunostaining. Results: The average diameter of LNC was 10.2±2.4 µm, which was significantly smaller than that of BMMSC (14 ±3.4 µm) (p<0.0001). Expression of 20,432 genes was examined by Gene Expression Array, among which expression of 349 genes in LNC was 10-fold or higher than that of BMMSC and expression of 8 genes in LNC was 100-fold or higher than that of BMMSC, while expression of 3 genes in BMMSC was 100-fold higher than that of LNC. GO analysis and pathway analysis showed that the differentially expressed genes were mainly enriched in the extracellular matrix receptor interaction pathway and Wnt signaling pathway. In addition, RT-qPCR results demonstrated that the expression of CD73, CD90, CD105, PDGFRß, Vimentin, SCF, KIT (CD117), COL14A1, LAMA2, THBS2, FZD1, BMP2 and CXCL12 genes in LNC were at least 2 folds higher than BMMSC. The protein level of LAMA1 was higher but the protein level of COL4A1 was lower in LNC than that in BMMSC. Conclusion: LNC exhibit differential gene expression from BMMSC in the extracellular matrix (ECM) receptor interaction pathway and Wnt signaling pathway, suggesting that LNC have their unique signaling pathways to support limbal stem cell niches.

Polyoxovanadate-iodobodipy supramolecular assemblies: new agents for high efficiency cancer photochemotherapy.

Two novel polyoxovanadate-iodoBodipy supramolecular assemblies, named as (2I-BDP-C6)2V6 and (2I-BDP-C6)3V10, were first synthesized by the self-assembly of anionic hexavanadate and decavanadate with cationic iodoBodipy for photochemotherapy, respectively. The mechanisms for synergistic photochemotherapy of the anion-cation pairs were determined. In particular, (2I-BDP-C6)3V10 can effectively kill lung cancer cells (HepG2) by synergetic chemotherapy as well as photodynamic therapy.