1.Recent developments in lacrimal gland research and its implications in dry eye
Chinese Journal of Experimental Ophthalmology 2020;38(10):877-880
The lacrimal gland, as an essential component of the ocular surface system, along with its product, the tears, had not received sufficient attention in the past years.However, increasing evidence suggest that the lacrimal gland plays a critical role in maintaining the normal function of the eyes, and disruption of its function may lead to dry eye.In this review, the author tried to summarize the recent developments in lacrimal gland research and its role in the etiology and development of dry eye, particularly with our own research findings from lacrimal gland ducts.The author believes that more efforts should be directed to the lacrimal gland research, especially the ion transporters/channels in the lacrimal gland duct system, which may be used as targets in developing novel treatments for dry eye.
2.Association between LIPC gene polymorphisms and choroidal neovascularization
Ling LIAO ; Fang HAO ; Dan JIANG ; Lulin HUANG ; Haoyu CHEN ; Zhenglin YANG
Chinese Journal of Experimental Ophthalmology 2020;38(10):845-850
Objective:To investigate the association between choroidal neovascularization (CNV) and the LIPC gene single nucleotide polymorphism (SNP) in a Chinese Han population from Shantou. Methods:A case-control study was designed.Two hundred and twenty-one patients with CNV who visited Shantou International Eye Center from January 2010 to December 2016 were enrolled and served as the CNV group, and 430 healthy volunteers matched in age and gender were enrolled and served as the normal control group.Each of 5 ml fasting peripheral blood of the subjects was extracted, and peripheral blood DNA was extracted after anticoagulation.PCR amplification was conducted on SNP loci of LIPC gene including rs10468017, rs920915 and rs2070895.After purification, genotyping was performed on the above SNP loci using the single base extension (SNaPshot) method.Hardy-weinberg equilibrium (HWE) test was used to determine the genotype frequency of the three SNPs of LIPC gene.The gene frequency and genotype frequency of the 3 loci between the CNV group and normal control group were compared.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong (No.11-004). Results:The genotype frequency distribution of rs10468017, rs920915 and rs2070895 of the three SNPs of LIPC gene reached genetic balance in the total samples ( P>0.05). The genotype frequencies of rs10468017 TT genotype, rs920915 CC genotype and rs2070895 AA genotype in CNV group were 3.62%, 5.43% and 12.22%, respectively, while those of normal control group were 2.56%, 5.58% and 14.19%, respectively, with no statistically significant difference (all at P>0.05). The minimum allele (T) frequency of rs10468017 was 18.1% and 17.2%, the minimum allele (C) frequency of rs920915 was 21.7% and 23.1%, and the minimum allele (A) frequency of rs2070895 was 33.7% and 38.7% in the CNV group and the normal control group, respectively (all at P>0.05). The odd ratio ( OR) values (95%confidence interval [ CI]) of rs10468017, rs920915 and rs2070895 in the CNV group and the normal control group were 1.06 (0.79-1.44), 0.92 (0.70-1.21) and 0.80 (0.63-1.02), respectively. Conclusions:The results from the present study do not indicate the association of LIPC SNPs (rsl0468017, rs920915 and rs2070895) with CNV in the Shantou Han population.
3.Analysis of National Natural Science Foundation of China grant support for basic research of ophthalmology during the past ten years
Xiuhua WANG ; Yongguang YANG ; Meng ZHANG ; Bo LEI
Chinese Journal of Experimental Ophthalmology 2020;38(10):864-870
Objective:To review the detail data of National Natural Science Foundation of China (NSFC) grant support during past decade and to analyze the tendency of basic and applied science researches in ophthalmology and vision science.Methods:The detail data of grants supported by NSFC in the field of ophthalmology and vision science during 2010—2019 were collected.The project category, project name, principle investigator, amount of grant, supported institute and region distribution were analyzed.Cluster analysis of key words associated with the projects was performed with VOSviewer software.Results:During the past decade, the number of projects and the total amount of funding from NSFC were stable in ophthalmology and vision science, which accounted for about 2% of medicine field.The number of keywords representing advanced researches, hotspots areas and methodologies increased.Retinal and choroidal diseases, corneal and ocular surface diseases, glaucoma and optic nerve diseases ranked in the top three in the granted projects.Granted projects mainly went to the well-developed areas in economy and education.The high-level talent projects primarily were in the institutes and universities with solid and profound scientific research background.Conclusions:The sustained and stable support of NSFC plays a promoting role in the development of ophthalmology and vision science and talent cultivation.The new technology and its integration with interdisciplinary science promote the development of ophthalmology.Successfully granted projects appear to be related to the regional environment of economy, education and scientific research background.
4.Corneal endothelial cell density and morphology of cataract eyes in Danzhou city Hainan province
Jing HUANG ; Yali DU ; Mingzhi ZHANG
Chinese Journal of Experimental Ophthalmology 2020;38(10):858-863
Objective:To describe corneal endothelial cell density and morphology in cataract eyes in Danzhou city, Hainan province and analyze the influencing factors.Methods:A cross-sectional study was performed.A total of 573 eyes of 573 cataract patients at Danzhou First People's Hospital, one of the Poverty Reduction Eye Centres of "Project Vision" , were enrolled from February to December in 2009.TOPCON non-contact corneal endothelial microscope was performed to measure the endothelial cell density, corneal central thickness (CCT), average endothelial cell area, maximum endothelial cell area, minimum endothelial cell area, cell area standard deviation, coefficient of variation in cell area, and percentage of hexagonality.The differences of the above parameters were compared among different genders, eyes and age groups, and the influencing factors were analyzed.This study followed the Declaration of Helsinki.Written informed consent was obtained from each subject prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong (No.09-007).Results:The average endothelial cell density of cataract patients was (2 533.00±366.674)/mm 2 (from 846 to 3 969/mm 2), and the CCT was (501.150±31.666) μm.Age ( P<0.01), CCT ( P=0.013), maximum endothelial cell area ( P=0.017), endothelial cell area standard deviation ( P=0.011), coefficient of variation in endothelial cell area ( P=0.001), percentage of hexagonality ( P<0.01), and average endothelial cell area ( P<0.01) were the major influencing factors of endothelial cell density.Endothelial cell density was significanly different in any two age groups (all at P<0.05). The endothelial cell density in cataract patients of 60-79 years old group and ≥80 years old group was lower than that of <60 years old group, whereas the endothelial cell density in patients ≥80 years old subgroups was higher than that in the 60-79 years subgroup, and the difference was statistically significant (all at P<0.01). Gender ( P<0.01), endothelial cell area standard deviation ( P=0.030), coefficient of variation in endothelial cell area ( P=0.012) and endothelial cell density ( P<0.01) were the main influencing factors of CCT.The CCT was (516.27±35.84)μm in male patients, which was significantly higher than (492.20±24.97)μm in female patients, the difference was statistically significant ( t=89.205, P<0.01). The difference of other parameters between different genders was not statistically significant ( P>0.05). There was no significant difference in corneal endothelium parameters between right and left eyes ( P>0.05). Conclusions:Corneal endothelial cell density varies with age, coefficient of variation in cell area, average endothelial cell area and percentage of hexagonality in cataract patients in Danzhou city.The aging degree of corneal endothelial cell is different in patients older than 60 years.
5.A comparison of postoperative efficacy and safety between laser-assisted subepithelial keratomileusis versus femtosecond laser assisted in situ keratomileusis for high myopic eyes
Mingna LIU ; Hua GAO ; Na LI ; Weiyun SHI
Chinese Journal of Experimental Ophthalmology 2020;38(10):851-857
Objective:To evaluate and compare the safety, efficacy, stability and predictability of laser-assisted subepithelial keratomileusis (LASEK) with femtosecond laser assisted in situ keratomileusis (FS-LASIK) for high myopic eyes.Methods:A non-randomized controlled clinical study was performed.The clinical data of 141 eyes of 75 patients who received LASEK or FS-LASIK for high myopia in Shandong Eye Hospital from January 2013 to December 2016 with complete medical data during 1-year following-up.The 56 eyes with the preoperative diopter of (-8.29±1.64)D received LASEK (LASEK group), and the 85 eyes with the preoperative diopter (-7.97±1.38)D underwent FS-LASIK (FS-LASIK group). Pre- and post-operative best corrected visual acuity (BCVA) and post-operative uncorrected visual acuity (UCVA) were recorded, and the spherical equivalent was examined by subjective optometry.The efficacy index, safety index, refractive stability, predictability and complications were assessed 6 months and 12 months after surgery.Efficacy index was defined as postoperative UCVA/preoperative BCVA; safety index was postoperative BCVA/preoperative BCVA; refractive stability was the difference of spherical equivalent between postoperative 6 months and 12 months, and predictability was the percentage of the eyes with the diopter ≤±0.50 D after surgery.This study protocol was approved by the Ethic Committee of Shandong Eye Hospital (No.SDSYKYY20180130).Results:There were no significant differences in efficacy index and safety index in both LASEK group and FS-LASIK group at 6 months and 12 months after surgery (all at P>0.05). The spherical equivalent was (0.08±0.30)D and (0.10±0.38)D in the LASEK group and (0.00±0.32)D and (0.01±0.35)D in the FS-LASIK group at 6 months and 12 months after surgery, and there were no significant differences between different time points in both LASEK group and FS-LASIK group ( t=0.376, P>0.05; t=0.227, P>0.05), showing a good refractive stability.At 12 months after surgery, the percentage of the eyes with spherical equivalent within ±0.50 D was 91.1% in the LASEK group and 96.4% in the FS-LASIK group, there was no significant difference between the two groups ( χ2=1.838, P>0.05). Four eyes in the LASEK group developed corneal haze at 12 months after the operation, and the postoperative BCVA was less than the preoperative BCVA. Conclusions:Both LASEK and FS-LASIK are safe, effective, stable and predictable for the correction of high myopic eyes.Corneal haze after LASEK is the main reason for the loss of BCVA.
6.The importance of basic research and drug development for thyroid-associated ophthalmopathy
Chinese Journal of Experimental Ophthalmology 2020;38(11):905-909
Thyroid-associated ophthalmopathy (TAO) is an organ specific autoimmune disease with complex pathogenesis.In recent years, great progress has been made in the pathogenesis of TAO primarily in immune and molecular mechanism aspects, including related autoantigens, lymphocytes, inflammatory factors, and autoimmune target tissue, that is, the role and biological behavior of orbital fibroblasts.Accordingly, various biological agents and immunosuppressive agents have emerged in an endless stream and have shown good effects and safety in clinical trials.Some important researches seem to be promising, but many novel therapies still are not extensively applied in clinical practice up to now.Therefore, it is of great significance to strengthen the basic research of TAO, fully understand its pathogenesis, research and develop more targeting drugs and precise clinical diagnosis and management of TAO, as well as improve the prognosis of patients.
7.Paying close attention to advanced researches of ocular surface mucin and significance in the diagnosis and management of dry eye
Chinese Journal of Experimental Ophthalmology 2020;38(11):910-915
As an important part of the tear film, mucin can be divided into secretory mucin and membrane-associated mucin according to different functions.Secretory mucin, secreted by goblet cells, plays a key role in maintaining the stability of the tear film, antimicrobial properties and ocular surface protection.Membrane-associated mucin, expressed by corneal conjunctival epithelium, plays a key role in maintaining the stability of the tear film, barrier, and signal transduction.Quality or quantity abnormal of mucin may damage the stability of tear film, leading to dry eye.While dry eye may damage the integrity of the epithelium of ocular surface, resulting in exacerbation of mucin abnormalities.The detection methods of mucin include tear ferning test, ocular surface staining, impression cytology, confocal microscopy, tear break-up time, and quantitative detection of mucin.P2Y2 receptor agonists and mucin secretion agonists can improve mucin secretion.Ophthalmologists should understand the basic characteristics and functions of ocular surface mucin and pay close attention to current clinical examination and its association with dry eye in order to push forward the related study and develop the precise diagnosis and therapeutic methods for mucin deficiency dry eye as well as the comprehensive therapies of mixed type, midrate to severe dry eye and immune-associated dry eye.
8.Stability evaluation of different internal fixation methods for zygomaticomaxillary complex fractures by finite element biomechanical analysis
Yan LI ; Pengsen WU ; Yue MA ; Meiting TANG ; Xueying ZENG ; Yuanyuan TANG ; Shen YU ; Wei LU
Chinese Journal of Experimental Ophthalmology 2020;38(11):916-922
Objective:To analyze the stability of different internal fixation methods for zygomaticomaxillary complex fracture using finite element biomechanical analysis and to provide a quantitative basis for the option of optimal internal fixation methods.Methods:One patient with zygomaticomaxillary complex ZMC fracture (Zingg B type) was enrolled from the Second Hospital of Dalian Medical University in October 2016.The zygomaticofrontal suture and the inferior orbital rim were fixed during the surgery, and the postoperative function was well recovered with no mouth opening restriction, diplopia or implant displacement, and had a symmetrical facial appearance.The preoperative orbital CT images were collected.The normal craniofacial bones finite element model (FEM/intact) was reconstructed through Mimics, Geomagic, Solidworks and Abaqus softwares based on the non-fractured side and verified.Based on the verified model, the segmentation and assembling was performed according to the fracture location, and the internal fixation models were established according to the methods of surgery, including fixed zygomaticofrontal suture model (FEM/ZFS), fixed inferior orbital rim model(FEM/IOR), fixed zygomaticofrontal suture and inferior orbital rim model (FEM/ZFS+ IOR), fixed ZFS and IOR and zygomaticomaxillary suture model (FEM/ZFS+ IOR+ ZMS). The masseter muscle strength was applied to the model.The stress and displacement were analyzed and the rotation angle of zygoma was calculated to compare the stability of different operative methods.The postoperative model (FEM/post) was established according to the actual operative method and was compared with FEM/ZFS+ IOR.This study protocol was approved by the Ethic Committee of The Second Hospital of Dalian Medical University (2020-33), and written informed consent was obtained from the subject before entering the study.Results:The established FEM/intact had a realistic appearance and good geometric similarity, and the validity and accuracy of model was verified.In the FEM/ZFS+ IOR and FEM/ZFS+ IOR+ ZMS, the maximal stress of the titanium plate was 396 MPa and 426 MPa, respectively, which was lower than the yield strength 483 MPa of pure titanium, and the maximal displacement of the fracture line was 0.10 mm and 0.06 mm, respectively, which was both≤0.1 mm, and the rotation angle of zygoma was both<2°.In the FEM/ZFS and FEM/IOR, the maximal stress of the titanium plate was 730 MPa and 501 MPa, respectively, which was higher than the yield strength of pure titanium; the maximal displacement of fracture line was 0.27 mm and 0.15 mm, respectively, which was >0.1 mm, and the rotation angle of zygoma was <2°.The results of FEM/post were consistent with those of FEM/ZFS+ IOR.Conclusions:The finite element analysis can perform digital analysis and evaluation of the stability of different internal fixation methods before surgery, which is available for the selecting of the optimal fixation methods.Finite element analysis can provide an objective quantitative basis for the precise treatment of zygomaticomaxillary complex fractures.
9.Effects of IL-17A and IFN-γ on the fibrosis of CD34 - orbital fibroblasts in Graves orbitopathy
Yi LU ; Yazhuo HUANG ; Yinwei LI ; Yu WU ; Sijie FANG ; Jing SUN ; Huifang ZHOU
Chinese Journal of Experimental Ophthalmology 2020;38(11):923-928
Objective:To observe the effects of interleukin-17A (IL-17A) and interferon-γ (IFN-γ) on CD34 - orbital fibroblasts (OFs) in patients with Graves ophthalmopathy (GO), and to explore the pathogenesis of GO. Methods:Orbital adipose connective tissue and lacrimal gland tissue of 5 patients with GO were collected during orbital decompression surgery.These tissue was cultured by tissue explant culture method.CD34 - OFs were enriched by immunomagnetic beads after passage and expansion.The cultured cells were divided into transforming growth factor-β (TGF-β) group, TGF-β+ 10 ng/ml IL-17A group, TGF-β+ 100 ng/ml IL-17A group, TGF-β+ 1 ng/ml IFN-γ group and TGF-β+ 5 ng/ml IFN-γ group.The fibrosis of the cells was induced with 5 ng/ml TGF-β and then was treated with different concentrations of IL-17A or IFN-γ according to grouping.The expression of fibronectin, collagen type Ⅰ, α-smooth muscle actin (α-SMA) and tissue metalloproteinase inhibitor-1 (TIMP-1) in CD34 - OFs derived from both orbital adipose connective tissue and lacrimal gland tissue were detected by Western blot.This study protocol was approved by an Ethic Committee of Shanghai Ninth People's Hospital (SH9H-2020-TK195-1) and written informed consent was obtained from each patient. Results:For CD34 - OFs derived from orbital adipose connective tissue, the relative expressions of fibronectin, type Ⅰ collagen, α-SMA and TIMP-1 protein were significantly higher in the TGF-β+ 100 ng/ml IL-17A group than those in the TGF-β group and TGF-β+ 10 ng/ml IL-17A group (all at P<0.05); the relative expressions of fibronectin, type Ⅰ collagen and α-SMA in the cells in the TGF-β+ 5 ng/ml IFN-γ group were significantly lower than those in the TGF-β group and the TGF-β+ 1 ng/ml IFN-γ group (all at P<0.05). For CD34 - OFs derived from lacrimal gland, the relative expressions of fibronectin, type Ⅰ collagen, α-SMA and TIMP-1 protein in the TGF-β+ 100 ng/ml IL-17A group were significantly higher than those in the TGF-β group and the TGF-β+ 10 ng/ml IL-17A group (all at P<0.05); the relative expressions of fibronectin, type Ⅰ collagen and TIMP-1 protein in the TGF-β+ 1 ng/ml IFN-γ group were significantly higher than those in the TGF-β group and TGF-β+ 5 ng/ml IFN-γ group, and the relative expression of α-SMA protein was significantly higher than that in the TGF-β+ 5 ng/ml IFN-γ group (all at P<0.05). Conclusions:High level of IL-17A can promote the fibrosis of TGF-β-induced CD34 - OFs, and high level of IFN-γ inhibits the fibrosis of TGF-β-induced CD34 - OFs.
10.Inhibitory effects of resveratrol on high glucose-induced apoptosis of retinal cells
Qingchun LI ; Dai LI ; Yiqiao XING
Chinese Journal of Experimental Ophthalmology 2020;38(11):929-935
Objective:To investigate the inhibitory effects of resveratrol (Res) on the apoptosis of retinal neurons of diabetic rats and ARPE-19 cells induced by high glucose.Methods:Streptozotocin was intraperitoneally injected to establish a diabetes model in 25 adult male SD rats, and 20 successful models were randomized into diabetic model group and Res-administered group according to random number table method.Another 10 matched normal rats were served as normal control group.Res was intragastrically given to the rats in the Res-administered group with the dose of 40 mg/(kg·d), and an equivalent volume of normal saline solution was used in the same way in the diabetic model group and normal control group.The body weight and blood glucose level were measured on the 0th, 4th, 8th, 12th week of administration.The rats were sacrificed on the 12th week by over-anesthesia and the eyeballs were enucleated.The ultrastructure of the retinal ganglion cells (RGCs) were examined under the transmission electron microscope.The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was to assess the apoptosis of retinal neurons.ARPE-19 cells were divided into normal control group, high glucose group and Res-treated group and cultured for 48 hours in medium containing 5.5 mmol/L glucose, 30 mmol/L glucose, 30 mmol/L glucose and 10 mol/L Res, respectively.Apoptosis rate was detected by a flow cytometry.The distribution and expression of bax and bcl-2 in the cells was detected by immunofluorescence and Western blot assay, respectively.This study protocol was approved by an Experimental Animal Ethic Committee of Hubei University of Science and Technology, and the use and care of the animals complied with the Statement of ARVO.Results:Compared with the diabetic model group, the body weight was increased at 4-12 weeks and the blood glucose level was lowered at 8-12 weeks of Res administration in the Res-administered group (both at P<0.01). The chromatin condensation, mitochondrial swelling and vacuolation in cytoplasm were obviously slight and the apoptosis rate was reduced in the Res-administered group in comparison with the diabetic model group.The apoptosis indexes of the retinal ganglion cell layer cells and inner nuclear layer cells in the Res-administered group were (18.36±3.37)% and (23.67±8.98)%, respectively, which were significantly lower than (83.91±9.8)% and (64.26±10.66)% in the diabetic model group (both at P<0.01). The apoptosis rate of the ARPE-19 cells in the normal control group, high glucose group and Res-treated group was (3.11±0.26)%, (11.41±1.06)% and (5.38±0.58)%, respectively, and the apoptosis rate in the Res-treated group was significantly lower than that in the high glucose group (all at P<0.01). Immunofluorescence assay showed that the fluorescence of bax in the cell nucleus of Res-treated group was obviously enhanced in comparison with the normal control group and weaker in comparison with the high glucose group.The fluorescence of bcl-2 protein in the Res-interfered group was weaker in comparison with the normal control group and enhanced in comparison with the high glucose group.The relative expressions level of bax protein in the Res-treated group was 0.21±0.08, which was significantly higher than 0.15±0.06 in the normal control group and lower than 0.31±0.09 in the high glucose group (both at P<0.05). The relative expressions of bcl-2 protein was 0.66±0.25 in the Res-treated group, which was significantly lower than 0.80±0.14 in the normal control group and higher than 0.23±0.09 in the high glucose group (both at P<0.05). The bcl-2/bax ratio in the Res-treated group was significantly higher than that in the high glucose group ( P<0.01). Conclusions:Res can inhibit the apoptosis of RGCs of diabetic rats and high glucose-induced RPE cells in vitro.