Hemorrhagic retinal arterial macroaneurysm combined with branch retinal artery occlusion treated with intravitreal conbercept injection: A case report.

RATIONALE: Branch retinal artery occlusion (BRAO) is a rare complication of retinal arterial macroaneurysm (RAM), a low-incidence ocular disease. PATIENT CONCERNS: A 75-year-old woman presented with a chief complaint of blurred vision. DIAGNOSES: The patient for 4 days received a diagnosis of RAM combined with BRAO. INTERVENTIONS: The patient was treated with two successive intravitreal conbercept injections. OUTCOMES: The patient's best-corrected visual acuity improved, and the RAM diminished. LESSONS: Administration of conbercept injection might be an effective treatment for complex RAM with BRAO.

KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract.

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

PDLIM1 inhibits cell migration and invasion in diabetic retinopathy via negatively regulating Wnt3a.

The injury of vascular endothelial cells is a crucial factor in the development of diabetic retinopathy (DR). PDLIM1 (a member of the PDZ and LIM protein family) has been reported to exert an essential function in vascular diseases. This study aimed to elucidate the role of PDLIM1 on retinal vascular endothelial cells in DR. Immunofluorescence staining was used to localize the expression of PDLIM1 in the mouse retina. In some tumor diseases, PDLIM1 has been reported to play a key role in regulating the Wnt pathway. However, no in-depth reports have been found in DR. Retinal capillary endothelial cells (RCECs) were treated with high-glucose and high-lipid (HG/HL) culture medium, and siRNA transfection to investigate the role of PDLIM1 in DR. PDLIM1 and Wnt3a expression was confirmed by qRT-PCR and western blotting. Flow cytometry, Transwell assay, and scratch assay were used to test the ability of cell apoptosis, migration, and invasion. PDLIM1 was mainly expressed in the retinal pigment epithelium (RPE), ganglion cell layer (GCL), inner plexus layer (IPL), and outer plexus layer (OPL). HG/HL increased Wnt3a levels and promoted cell's ability of apoptosis, migration, and invasion, which were reversed by the knockdown of PDLIM1. PDLIM1 was found to play a protective role in diabetic retinopathy by counter-regulating Wnt3a. PDLIM1 ameliorates cell apoptosis, migration, and invasion by negatively regulating Wnt3a in RCECs of DR, which suggests that PDLIM1 might be a promising therapeutic target for DR treatment.

Therapeutic potential of pupilloplasty combined with phacomulsification and intraocular lens implantation against uveitis-induced cataract.

AIM: To evaluate the therapeutic effect of pupilloplasty combined with phacomulsification and intraocular lens implantation (PPI) in uveitis-induced cataract. METHODS: Total 28 patients with uveitis-induced cataract were enrolled. Within 3mo before the PPI, 7 cases accompanied with glaucoma maintained carteolol hydrochloride for lowering intraocular pressure, and 1 case maintained glucocorticoid for anti-inflammation. The baseline characteristics, treatment processes, and outcomes of enrolled cases were retrospectively analyzed. Hematoxylin and eosin (HE) staining was performed to reveal the histopathological changes of iris tissues. RESULTS: Iris hemorrhage was the only intraoperative complication observed in 2 cases. After the surgery, normal intraocular pressure, right position of intraocular lens, and improved visual gain [best corrected visual acuity (BCVA)>0.5] were achieved. Postoperative keratic precipitates was observed in 2 cases, which was recovered within 1wk. During the follow-up of 5-10y, no recurrence of uveitis was found in 27 cases (96.43%). Uveitis only recurred in one case with the onset of ankylosing spondylitis. HE staining showed iris stroma (all samples), pigment cell hyperplasia in pigment epithelium (n=9) and stroma (n=19), inflammatory cell infiltration in iris (n=7), and neovascularization in iris surface (n=2). CONCLUSION: PPI improves the visual gain and prevents the long-term recurrence of uveitis in patients with uveitis-induced cataract, including those with preoperative intraocular pressure abnormality (glaucoma) and inflammation (active uveitis). Uveitis presents stroma atrophy, pigment cell hyperplasia, and inflammatory cell infiltration, even in a quiet state.

Remotely Controlling Drug Release by Light-Responsive Cholesteric Liquid Crystal Microcapsules Triggered by Molecular Motors.

Stimuli-responsive smart nanocarriers are an emerging class of materials applicable in fields including drug delivery and tissue engineering. Instead of constructing responsive polymer shells to control the release and delivery of drugs, in this work, we put forward a novel strategy to endow the internal drugs with light responsivity. The microcapsule consisted of molecular motor (MM)-doped cholesteric liquid crystals (CLCs) and drugs. The drug in gelatin-gum arabic microcapsules can protect the carried drugs for a long time with a low release speed totally resulting from drug diffusion. Under UV light, the MM isomerizes and the chirality changes, inducing the alteration of the superstructure of the CLCs. In this process, the cooperative molecular disturbance accelerates the diffusion of the drugs from the microcapsule core to the outside. As a result, thanks to the cooperative effect of liquid crystalline mesogens, molecular-scale geometric changes of motors could be amplified to the microscale disturbance of the self-organized superstructure of the CLCs, resulting in the acceleration of the drug release. This method is hoped to provide opportunities in the design and fabrication of novel functional drug delivery systems.

Integrating network pharmacological and experimental models to investigate the therapeutic effects of baicalein in glaucoma.

BACKGROUND: Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism. METHODS: Network pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation. RESULTS: The results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma. CONCLUSION: By combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.

Whole-exome sequencing identifies an RS1 variant in a Chinese family with X-linked retinoschisis.

A notable behavioural feature of X-linked retinoschisis (XLRS) is extensive structural schisis (splitting) of the outer plexiform and inner nuclear layers of the neurosensory retina, which is partly combined with complications related to vitreous hemorrhage, macular holes and retinal detachment. The present study aimed to identify the pathogenic gene mutation in a three-generation Chinese family with XLRS by whole-exome sequencing (WES). The clinical information of a three-generation Chinese family with cases of XLRS was collected. WES was performed for the proband. A comparison with the human reference genome sequence (hg38) and bioinformatic analysis were performed to reveal putative variants and Sanger sequencing was applied to verify mutations in this family and healthy control participants. Intraretinal cystic spaces were detected by optical coherence tomography imaging. Structures of the wild-type and mutant retinoschisin 1 (RS1) protein were modelled by PyMol. Almost all patients had a history of vision loss and abnormal blue-purple colour vision; however, the phenotypes of the 4 patients were distinctly different. There was no linear correlation between phenotypic severity and age. A recurrent RS1 (Xp22.2) mutation (NM_000330: c.559C>T) was detected, resulting in the p.Q187X variant. According to the protein model, this variant is likely pathogenic. The present study was the first to report that RS1:c.559C>T induces XLRS in a three-generation Chinese pedigree, with the mutation leading to premature termination of translation of the RS1 protein. WES was able to diagnose XLRS, which has the characteristics of clinical and genetic heterogeneity.

Whole-exome sequencing identification of a recurrent CRYBB2 variant in a four-generation Chinese family with congenital nuclear cataracts.

Congenital cataracts is the most common cause of visual impairment and blindness in children. Although there have been extensive studies into the pathogenesis of congenital cataracts, the pathogenic mechanism underlying the recurrent variant CRYBB2:c.62T>A(p.I21N) has not been previously reported. Thus, the present study aimed to use whole-exome sequencing (WES) to identify potential genetic variants and investigate how they may have induced the occurrence of cataracts in a four-generation Chinese family with congenital nuclear cataracts. The medical history of this family was recorded and WES was conducted for one proband. Sanger sequencing was used to verify the presence of the putative variant in all participants. PolyPhen-2, SIFT and ProtScale were used to analyze the effect of the identified variants on protein function and hydrophobicity, and Pymol was used to show the structure of the wild-type (Wt) and mutant ß-crystallin B2 (CRYBB2) protein. Full-length Wt-CRYBB2 or mutant-CRYBB2 (I21N-CRYBB2) were fused to green fluorescent protein (GFP), and the recombinant plasmids were transfected into HeLa cells. Reverse transcription-quantitative PCR and western blotting were used to detect the expression levels of CRYBB2 mRNA and protein. Immunofluorescence and flow cytometry analyses were used to detect protein localization and apoptosis, respectively. A recurrent variant CRYBB2:c.62T>A(p.I21N) was identified in a four-generation Chinese family with congenital nuclear cataracts. Multiple-sequence alignment of CRYBB2 demonstrated that codon 21 was highly conserved. Pymol revealed that the structure of the I21N-CRYBB2 protein was distinct from that of Wt-CRYBB2. PolyPhen-2 predicted that it had a variant provean score 1.0, suggesting it was 'probably damaging', and SIFT predicted it had a variant provean score of -5.113, indicating it was 'deleterious'. ProtScale indicated that the hydrophobicity of the mutation site was significantly reduced. The protein expression levels of the I21N-CRYBB2 were decreased compared with the Wt-CRYBB2. Immunofluorescence analysis revealed that the variant I21N-CRYBB2 protein tended to accumulate around the nucleus, and flow cytometry analysis indicated that it increased cell apoptosis. Furthermore, I21N-CRYBB2 induced the activation of the unfolded protein response (UPR). In conclusion, a pathogenic variant of CRYBB2:c.62T>A(p.I21N) was identified via WES in a four-generation Chinese family with congenital nuclear cataracts. Through biological analysis, it was found that the variant induced abnormal protein aggregation, activated the UPR and triggered excessive cell apoptosis, which may lead to the occurrence of congenital nuclear cataracts in this family.

Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Qidengmingmu Capsule (QC) is a Chinese patent medicine used to treat DR, but the molecular mechanism of the treatment remains unknown. In this study, we identified and validated potential molecular mechanisms involved in the treatment of DR with QC via network pharmacology and molecular docking methods. The results of Ingredient-DR Target Network showed that 134 common targets and 20 active ingredients of QC were involved. According to the results of enrichment analysis, 2307 biological processes and 40 pathways were related to the treatment effects. Most of these processes and pathways were important for cell survival and were associated with many key factors in DR, such as vascular endothelial growth factor-A (VEGFA), hypoxia-inducible factor-1A (HIF-1Α), and tumor necrosis factor-α (TNFα). Based on the results of the PPI network and KEGG enrichment analyses, we selected AKT1, HIF-1α, VEGFA, TNFα and their corresponding active ingredients for molecular docking. According to the molecular docking results, several key targets of DR (including AKT1, HIF-1α, VEGFA, and TNFα) can form stable bonds with the corresponding active ingredients of QC. In conclusion, through network pharmacology methods, we found that potential biological mechanisms involved in the alleviation of DR by QC are related to multiple biological processes and signaling pathways. The molecular docking results also provide us with sound directions for further experiments.

Clinical characteristics of congenital lamellar cataract and myopia in a Chinese family.

To investigate the clinical characteristics and the genetic defect in a Chinese family with congenital lamellar cataract with myopia. Three generations of a single family were recruited in the present study. A detailed family history and clinical data were recorded. A total of 100 unrelated ethnically matched controls without family history of congenital cataracts and myopia were also recruited. Genomic DNA was extracted from peripheral blood leukocytes. The sequencing of candidate genes was performed to screen out the disease-causing mutation. The effects of amino acid changes on the structure of proteins were predicted by bioinformatics analysis. Affected individuals presented lamellar lens opacities and myopia. Direct sequencing revealed a heterozygous c. 34 C>T variation in the αA-crystallin protein (CRYAA) gene, which resulted in the replacement of a highly conserved arginine by cystine at codon 12 (p.R12C). This mutation co-segregated with all affected individuals and was not observed in unaffected members or the 100 normal controls. Bioinformatic analysis showed that a highly conserved region was located around Arg12, an increase in local hydrophobicity was shown around the substitution site and the secondary structure of the mutant CRYAA protein has been changed. This is the case of a congenital lamellar cataract phenotype with myopia associated with the mutation of Arg12Cys (p.R12C) in CRYAA. Our finding confirms the high rate of mutations at this dinucleotide. In addition, these results demonstrate a myopia susceptibility locus in this region, which might also be associated with the mutation in CRYAA.

Recurrent PAX 6 mutation in a Chinese family with congenital aniridia, progressive cataracts and mental retardation.

BACKGROUND: One prominent pathological feature of congenital aniridia is hypoplasia of the iris, often accompanied by other eye abnormalities. The objective of this study is to identify gene mutations responsible for autosomal dominance in a Chinese family with congenital aniridia, progressive cataracts and mental retardation. METHODS: A total of 11 family members, including 6 affected and 5 unaffected individuals were recruited. Whole exome sequencing was performed on the proband and Sanger sequencing was applied to identify the causal mutation in the other family members and control samples. RESULTS: A heterozygous mutation, c. 112delC (p. Arg38fs) in PAX 6, was identified in the family that was associated with congenital aniridia, progressive cataracts and mental retardation. The mutation was exclusively observed in all affected individuals but not in unaffected family members or unrelated healthy controls without aniridia recruited from Beijing Tongren Hospital. Bioinformatics analysis indicated that the mutation c. 112delC (p. Arg38fs) in PAX 6 affected sugar phosphate backbone construction, leading to half reduction of the full-length protein. Other symptoms such as lens opacity, keratitis, lens dislocation, ciliary body hypoplasia, foveal hypoplasia and mental development retardation were also observed in this family. CONCLUSION: These results provided a new insight into the effects of PAX 6 as a mutational hotspot, with a symptom complex that includes congenital aniridia, progressive cataracts and mental retardation. These findings suggested the cognitive treatment of PAX 6-mutated individuals could be considered earlier clinically, combined with medication or surgery of congenital aniridia and progressive cataracts.

Performance of femtosecond laser-assisted cataract surgery in Chinese patients with cataract: a prospective, multicenter, registry study.

BACKGROUND: This study aimed to investigate the completion rate, visual performance, and adverse outcomes of femtosecond laser-assisted cataract surgery (FLACS) in Chinese patients. METHODS: This is a prospective, single-arm, multicenter registry study of 19 cataract surgery clinics in China. Chinese patients with cataract who underwent FLACS using the Alcon LenSx® laser system in single eye (n = 1140) or both eyes (n = 201) were enrolled and data were collected between March 2015 and August 2016. Clinical characteristics were recorded before surgery, and on postoperative days 1, 7, and 30. For surgery on both eyes, the second eye was included in the analysis only if it was operated within 30 days after the first eye surgery. The primary outcome was the completion rate of circular anterior capsulotomy. Secondary outcomes for lens fragmentation, corneal incision, and intraocular lens (IOL) implantation included best corrected distance visual acuity (BCDVA) and completion rates. Adverse events (AEs) were recorded. RESULTS: The completion rates of circular anterior capsulotomy, lens fragmentation, corneal incision, and IOL implantation were 98.6% (95% CI: 97.8-99.1%), 99.5% (95% CI: 99.1-99.8%), 97.6% (95% CI: 96.7-98.3%), and 100% (95% CI: 99.8-100%), respectively. BCDVA preoperatively and at postoperative day 30 were 1.134 ± 0.831 logMAR and 0.158 ± 0.291 logMAR, respectively. The proportion of eyes with BCDVA of 20/20 or better was 1.6% at baseline and 41.3% at postoperative day 30. AE incidence was 0.32%, with posterior capsule rupture present in 0.19% of eyes. CONCLUSION: FLACS using the LenSx® laser system can achieve satisfactory results in a real-world setting.

A Prechop Technique Using a Reverse Chopper.

PURPOSE: To describe a manual prechop technique for splitting the nucleus of the lens using a recently developed reverse chopper. METHODS: During the process, the reverse chopper and the Nagahara chopper are placed diagonally in the peripheral area of the nucleus of the lens after capsulorhexis. The reverse chopper and the Nagahara chopper then are pushed horizontally toward each other so they meet at the center of the lens to split the nucleus of lens into 2 parts. RESULTS: In all cases, the reverse chopper was effective during the prechop procedure for hard nuclei, the nucleus of the lens remained in situ during the chopping process, and the reverse chopper did not retract the suspensory ligament in patients in whom the ligament was fragile. During the prechop procedure, no capsule breakage occurred, and the time and energy required for effective phacoemulsification were reduced significantly. CONCLUSIONS: The prechop technique using the reverse chopper can be applied for cases with grade III-V nuclei, overripe nuclei, and fragile suspensory ligaments. The procedure is simple, and the learning curve is not steep.

Antitumor efficacy of VP22-CD/5-FC suicide gene system mediated by lentivirus in a murine uveal melanoma model.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which has high frequency of metastasis to the liver, typically causing a fatal outcome. Chemo-resistance remains a major obstacle in the therapeutic approach to UM, leaving limited choice for treating UM. Other possible treatments have been explored but the results are yet to be evident. To improve therapy for UM, transcriptional suicide genes were transfected into the OCM-1 cell line. In the current study, OCM-1 cells transfected with lentiviral-meditated EGFP, cytosine deaminase (CD)/EGFP, and VP22-CD/EGFP were established. Of the three groups, we examined the cell growth in vitro and in vivo by using the MTT method with cell culture media and MRI in murine UM models. According to our results, the cell proliferation in the transfected CD/EGFP group was slower than the non-suicide gene group. The VP22-CD/EGFP group manifested superior cell cytotoxicity than the CD/EGFP group. Further analysis of MRI and fluorescent imaging of the murine UM model identified significant differences in tumor volume among the three groups. Collectively, our study demonstrated that CD/5-FC is a potent therapeutic approach for UM. With the efficacy of VP22, suicide gene-induced cytotoxicity was superior to applying CD alone. Taken together, we concluded that novel therapy with the VP22-CD suicide gene may further contribute to treatment of UM.

Combined Special Capsular Tension Ring and Toric IOL Implantation for Management of Astigmatism and High Axial Myopia with Cataracts.

AIM: This study aimed to compare the effects of toric intraocular lens (IOL) implantation with a capsular tension ring and toric IOL implantation only in patients with axial myopic astigmatism who had undergone cataract surgery. METHODS: Of 34 patients with axial myopia, 16 patients who had received IOL and capsular tension ring (CTR) implantation were included in the combined group and 18 patients who received toric IOL implantation only were included in the simple group. Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) were evaluated by measuring subjective refraction, residual astigmatism, and the toric IOL axis six months post-surgery. RESULTS: At six months postoperatively, the UCVA for the combined and simple groups was 4.6 ± 0.1 and 4.5 ± 0.2, respectively, a statistically significant difference (t = 3.531, P<0.05). The toric IOL in all of the cases was located in the capsular sac, but there were more cases with IOL rotation (12 eyes) in the simple group than in the combined group (4 eyes). The rotation angles were 20°~30° (one eye), 10°~20° (four eyes), and <10° (seven eyes) compared with 2°~5° (four eyes). The residual astigmatism was -0.50 ± 0.25 D in the combined group, not a significant difference from the predicted residual astigmatism (-0.35 ± 0.13 D). There was a significant difference in the simple group (-1.25 ± 0.33 D) when the predicted residual astigmatism was compared (-0.37 ± 0.11 D) (t = -9.511, P < 0.01). CONCLUSIONS: In patients with axial myopic astigmatism, CTR can effectively increase the rotational stability of a toric IOL, achieving improvement in corneal astigmatism and visual acuity.

Cyclodextrin-containing hydrogels as an intraocular lens for sustained drug release.

To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) hydrogels containing ß-cyclodextrin (ß-CD) (pHEMA/MMA/ß-CD) were designed and prepared as intraocular lens (IOLs) biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/ß-CD copolymers containing different ratios of ß-CD (range, 2.77 to 10.24 wt.%) were obtained using thermal polymerization. The polymers had high transmittance at visible wavelengths and good biocompatibility with mouse connective tissue fibroblasts. Drug loading and release studies demonstrated that introducing ß-CD into hydrogels increased loading efficiency and achieved the sustained release of the drug. Administering ß-CD via hydrogels increased the equilibrium swelling ratio, elastic modulus and tensile strength. In addition, ß-CD increased the hydrophilicity of the hydrogels, resulting in a lower water contact angle and higher cellular adhesion to the hydrogels. In summary, pHEMA/MMA/ß-CD hydrogels show great potential as IOL biomaterials that are capable of maintaining the sustained release of anti-inflammatory drugs after cataract surgery.

Comparison of hydrophobic and hydrophilic intraocular lens in preventing posterior capsule opacification after cataract surgery: An updated meta-analysis.

BACKGROUND: Posterior capsular opacification (PCO) is a common long-term complication of cataract surgery. Intraocular lens design and material have been implicated in influencing the development of PCO. This study evaluated the association of hydrophobic and hydrophilic intraocular lenses on preventing PCO. METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until August 3, 2016, using the following search terms: cataract, posterior capsule opacification, and intraocular lens. Eligible studies included randomized controlled trials (RCTs), retrospective, and cohort studies. RESULTS: Eleven studies were included in the study with a total of 889 eyes/patients. The overall analysis revealed that hydrophobic intraocular lenses were associated with lower Nd:YAG laser capsulotomy rates than hydrophilic lenses [odds ratio (OR) = 0.38, 95% confidence interval (95% CI) = 0.16-0.91, P = .029]. Hydrophobic intraocular lenses were also associated with lower subjective PCO score (diff. in means: -1.32, 95% CI = -2.39 to -0.25, P = .015) and estimated PCO score (diff. in means: -2.23; 95% CI, -3.80 to -0.68, P = .005) as compared with hydrophilic lenses. Objective PCO score was similar between lens types. (diff. in means: -0.075; 95% CI, -0.18 to 0.035; P = .182). Pooled analysis found that visual acuity was similar between hydrophobic and hydrophilic intraocular lenses (diff. in means: -0.016; 95% CI, -0.041 to 0.009, P = .208). CONCLUSION: In general, PCO scores and the rate of Nd:YAG laser capsulotomy were influenced by intraocular lens biomaterial. Lens made of hydrophobic biomaterial were overall superior in lowering the PCO score and the Nd:YAG laser capsulotomy rate, but not visual acuity.

Photothermal Ring Integrated Intraocular Lens for High-Efficient Eye Disease Treatment.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. So far, the only method for PCO treatment is the precisely focused laser surgery. However, it causes severe complications such as physical damages and neuron impairments. Here, a nanostructured photothermal ring integrated intraocular lens (Nano-IOLs) is reported, in which the rim of commercially available IOLs (C-IOLs) is decorated with silica coated Au nanorods (Au@SiO2 ), for high-efficient prevention of PCO after cataract surgery. The Nano-IOLs is capable of eliminating the residual lens epithelial cells (LECs) around Nano-IOLs under mild laser treatment and block the formation of disordered LECs fibrosis, which eventually leads to the loss of vision. The Nano-IOLs shows good biocompatibility as well as extraordinary region-confined photothermal effect. In vivo studies reveal that PCO occurrence in rabbit models is about 30%-40% by using Nano-IOLs, which is significantly lower than the control group that treated with C-IOLs (100% PCO occurrence) 30 d postsurgery. To the best of our knowledge, it is the first example to integrate nanotechnology with intraocular implants aiming to clinically relevant PCO. Our findings indicate that spatial controllability of photothermal effect from nanomaterials may provide a unique way to intervene the PCO-induced loss of vision.

rs78378222 polymorphism in the 3'-untranslated region of TP53 contributes to development of age-associated cataracts by modifying microRNA-125b-induced apoptosis of lens epithelial cells.

MicroRNAs (miRNAs) negatively regulate the expression of the target genes by binding to 'seed sequences' in the 3'­untranslated region (3'­UTR) mRNA transcripts, and the variants within or nearby 'seed sequences' may compromise or enhance miRNA/mRNA interaction leading to either 'loss­of­function' or 'gain­of­function' effects. Cataracts are the leading cause of blindness worldwide and are characterized by progressive aggregation and precipitation of lens proteins, and the development of age­related cataracts is associated with dysregulated cellular activities of lens epithelial cells. Luciferase assays and online miRNA databases were used to validate that tumor protein p53 (TP53) is the target gene of miR­125b. Furthermore, reverse transcription­quantitative polymerase chain reaction and western blotting were conducted to detect expression levels of miR­125b and TP53 in different groups of cells transfected with miR­125b mimics or inhibitors. In addition, flow cytometry analysis and the MTT assay were conducted to detect the effects of miR­125b on apoptosis and cell viability. The current study demonstrated that the rs78378222 polymorphism minor allele introduces a novel potential miR­125b binding site in the TP53 3'­UTR with a consecutive 8­bp perfect match, creating a 'gain­of­function' variant and affecting the regulation of TP53 expression. A luciferase assay demonstrated that transfection of lens epithelial cells with wild type TP53 3'­UTR significantly reduced the luciferase activity of the miR­125b overexpressing cells compared with scramble controls. In addition, the luciferase activity of miR­125b overexpressing cells transfected with the construct containing the rs78378222 polymorphism minor allele was also reduced compared with cells transfected with the wild type 3'­UTR. Furthermore, it was demonstrated that the expression level of miR­125 was comparable in epithelial cells from patients with age­associated cataracts and controls, whereas the expression level of TP53 was significantly higher in the cataract group compared with controls. Additionally, transfection with 50 nM miR­125b mimics markedly reduced the mRNA and protein expression levels of TP53 in the cultured lens epithelial cells, and miR­125b significantly induced apoptosis in the epithelial cells compared with negative control cells. In conclusion, TP53 was identified as a target of miR­125b, and the minor allele of the rs78378222 polymorphism promoted the miR-125b/TP53 mRNA interaction.

Tailored (meth)acrylate shape-memory polymer networks for ophthalmic applications.

The unique features of shape-memory polymers enables their use in minimally invasive surgical procedures with a compact starting material switching over to a voluminous structure in vivo. In this work, a series of transparent, thermoset (meth)acrylate shape-memory polymer networks with tailored thermomechanics have been synthesized and evaluated. Fundamental trends were established for the effect of the crosslinker content and crosslinker molecular weight on glass transition temperature, rubbery modulus and shape-recovery behavior, and the results are intended to help with future shape-memory device design. The prepared (meth)acrylate networks with high transparency and favorable biocompatibility are presented as a promising shape-memory ophthalmic biomaterial.