1.Research progress in the relationship of interferon-inducible protein-10 with ocular neovascular diseases
Chinese Journal of Experimental Ophthalmology 2017;35(9):852-856
Interferon-inducible protein-10 (IP-10) is a member of the ELR-CXC-chemokine family,a molecule which is paid close attention to current studies.IP-10 can inhibit neovascularization and exert its function on anti-fibrosis as it binds with CXCR3,the only specific receptor to IP-10.Accumulating evidences revealed that IP-10 also involved in the pathologic process of ocular neovascular diseases.It shows that IP-10 was closely associated with subclinical chronic inflammation and involved in the development of age-related macnlar degeneration (AMD),which would be used as a clinical biomaker to make a definite diagnosis of AMD.The IP-10/CXCR3 signal,expressed on the choroidal endothelial cells,had the ability of suppressing choroidal neovascularization.Moreover,the over expression of IP-10 in the lesions of AMD may be attributed to the induction efficacy of promoting anti-angiogenic factor expression,such as IP-10 by vascular endothelial growth factor.IP-10 had an important role in the pathogenic process of diabetic retinopathy (DR) and might be used as a new indicator to evaluate the severity and prognosis of DR.And IP-10 may have the ability to suppress proliferative DR by interrupting formation of new vessels and promoting fibrosis of new vessels.Experimental study showed that IP-10 can reduce corneal neovascularization by down-regulating the expression of proangiogenic cytokines indirectly and suppressing the migration of vascular endothelial cells and tubegenesis directly.IP-10 is involved in the development of retinopathy of prematurity and polypoidal choroidal vasculopathy.Given its unique biological characteristics,IP-10 is expected to be a molecular target to inhibit neovascularization in treatment for ocular neovascular diseases.This article reviews the recent progress in the studies on relationship between IP-10 and several common neovascular eye diseases.
2.Recent advances of cellular therapy for corneal graft rejection
Chinese Journal of Experimental Ophthalmology 2017;35(9):848-851
Immune rejection is the leading cause of graft failure,and the main way for preventing corneal graft rejection is the application of immunosuppressive drugs.However,in the recent years,cellular therapy has been a new research hotspot for its targeted effect and fewer side effect.A lot of researches showed that Treg cells which areimportant in inducing and maintaining immunological tolerance could directly induce immune tolerance in cornealtransplantation.In recent years,dendritic cells also are found to have a dual role in the immune system,except as antigen presenting cells to induce immune response.Immature or immunosuppressive cytokine-expressing dendritic cells can induce immune tolerance.Mesenchymal stem cells which have multiple differentiation potential can exert anti-inflammatory effects on immune cells and effectively inhibit organ transplant rejection in vitro and in vivo.As another hotspot besides Tregs,myeloid-derived suppressor cells can inhibit the proliferation of a broad range of immune cells (T and B cells,NK cells,and macrophages),induce T cells apoptosis,and even induce Tregs.This review provides an update of these four kinds of cells on their effects and developments in cellular therapy for experimental corneal graft rejection.
3.Analysis of meibomain gland change and ocular surface condition in age-related cataract population
Hua, YU ; Bing, LI ; Jingjing, WANG
Chinese Journal of Experimental Ophthalmology 2017;35(9):838-842
Background Meibomain gland is a specially differentiated sebaceous gland lying in the tarsus of upper and lower eyelid.The morphological changes of the gland is associated with a variety of ocular surface diseases.Studying the relationship of morphological and functional change of meibomain gland with ocular surface is of great significance.Objective This study was to observe the change of morphology,structure and function of meibomain gland over aging and investigate the assocation of meibomain gland abnormality with ocular surface.Methods A prospectively cases-observational study was performed.Ninety-three eyes of 93 patients with age-related cataract aged 45 and older were enrolled in Shanxi Eye Hospital from March to September 2016 under the informed consent.The patients were divided into 45 to 59-year group and ≥60-year group according to age or meibomian gland loss ≥ 1/3 group and meibomian gland loss < 1/3 group.The ocular anterior segment,lid margin,meibomian gland orifices and lipids traits were examined by slit-lamp microscope.The ocular surface symptoms were assessed and scored by Ocular Surface Disease Index (OSDI) scale.The break-up time of tear film (BUT),tear meniscus height,meibomian gland dropout degree,conjunctival hyperemia and corneal fluorescence staining scores were measured using ocular surface analyzer.Results No dry eye symptom was complained in all the subjects,and their OSDI scores were <12.No abnormal changes at the lid margin and the muco-cutaneous junction were observed.No abnormality of the meibomian gland orifices,the lipids traits and drainage was observed under the slit-lamp microscope.BUT was shortened in 42 eyes (45.16%);tear meniscus height was lowed in 52 eyes (55.91%);meibomian gland loss range was ≥1/3 in 58 eyes (62.27%).The meibomian gland loss scores were 1.65±0.79 in the 45 to 59-year group and 1.86±0.72 in the ≥60-year group,showing an insignificant difference between them (t =1.301,P =0.197).But when coming to the correlation analysis,a positive correlation was found between meibomian gland loss scores and age (rs =0.323,P=0.002),and no correlations were seen between age and BUT or tear meniscus height (rs =0.154,P =0.141;rs=-0.024,P =0.821).In addition,meibomian gland loss scores showed a negative correlation with mean BUT (rs =-0.251,P =0.015).The eye number of BUT abnormality in the meibomian gland loss ≥ 1/3 group was more than that in meibomian gland loss <1/3 group (P =0.018).Conclusions Meibomian gland loss is more serious over aging in middle aged and elderly population,and serious meibomian gland loss increases the risk of tear film instability.The early meibomain gland dysfunction-like signs occur prior to symptoms,which should raise concern in clinical work.
4.Inflammation-causing effects and mechanism of natural killer cells in experimental autoimmune uveitis rats
Mohan, LI ; Ning, BAO ; Dongwei, LIU ; Liming, TAO ; Zhengxuan, JIANG
Chinese Journal of Experimental Ophthalmology 2017;35(9):799-804
Background Experimental autoimmune uveitis (EAU) is a common animal model of uveitis.Natural killer (NK) cells have been confirmed to be a type of strong inflammation-causing cells,but its role in EAU is still studing.Objective This study was designed to explore the role and mechanism of NK cells in the pathogenesis of EAU.Methods Thirty-six SPF Lewis rats were randomly divided into expeimental control group and EAU 6-,9-,12-,16-,and 21-day groups (6 rats for each group).Rats in EAU group received subcutaneous injection interphotoreceptor retinoid binding protein (IRBP) combining 5 mg/ml tubercle bacillus with complete Freund's adjuvant (CFA) emulsion in foot pads,and then 400 ng pertussis toxin was intraperitoneally injected to extablish EAU models in the EAU 6-,9-,12-,16-,and 21-day group,and normal saline solution combined with CFA and 400 ng pertussis toxin was used in the same way in the experimental control group.The inflammatory response was observed by slit lamp daily after modeling and scored based on Caspi criteria.The eyeballs were extracted in 6,9,12,16 and 21 days after modeling for retinal histopathological examination,Immunofluorescent double-staining was employed to detect and locate the expression of NK cells in the retina.In addition,25 model rats were divided into EAU 0-,3-,6-,9-and 12-day groups,with 5 rats for each group,and eyeballs were extracted to prepare tissue homogenate.The expression of CXCL10 mRNA,and CXCL12 mRNA NK cell chemokines,in the tissue homogenate was assayed by real-time quantitative PCR.The use and care of the rats followed Regulations for the Administration of Affair Concerning Experimental Animal by State Science and Technology Commission.Results No inflammatory sign in ocular anterior segment of the rats was seen in the experimental control group.The expansion of rat iris vessels was found in the EAU 6-day group,and exudes and hypopyon of the anterior chamber occurred in the EAU 9-day group and the inflammation peaked in the EAU 12-day gorup.The rat retinal structure was normal in the experimental control group,and the arrangement disorder of retinal structure,the cell separation in outer nuclear layer and damage of photoreceptors were found under the optical microscope in different degree in various EAU groups,with the most serious change in the EAU 12-day group.Immunofluorescent double staining showed normally arranged nucleus in the experimental control group,and a lot of NK infiltration was seen in the EAU 6-day group and peaked in the EAU 9-day group.The expression level of CXCL10 mRNA in the EAU 9-day group was 34.298 ± 16.689,which was significantly higher than that in the EAU 3-,6-and 12-day group,respectively (1.390 ± 0.660,3.359 ± 2.581,4.711 ±1.387) (all at P<0.01).No significant differences were found in the relative expression of CXCL12 mRNA among different EAU groups (F=2.851,P>0.05).Conclusions Retinal NK cell infiltration occurs in the early stage of EAU,and the severity of NK cell infiltration is consistent with the inflammatory process and CXCL10 expression,suggesting NK cells play an important role in the early stage of EAU,and CXCL10 is an important chemokine of NK cells in EAU rats.
5.Dynamic expression and mechanism of γδ T cells in the spleen of mouse with experimental autoimmune uveitis
Beibei, WANG ; Qingmei, TIAN ; Xiaofeng, XIE ; Jike, SONG ; Hongsheng, BI
Chinese Journal of Experimental Ophthalmology 2017;35(9):793-798
Background Previous studies showed that the pathogenesis of uveitis is related to γδ T cells.However,it remains unclear that how these cells are involved in experimental autoimmune uveitis (EAU).Objective This study aimed to observe the dynamic changes of γδ T cells in EAU and explore the role of γδ T cells in the pathological process of EAU.Methods Forty-five C57BL/6(B6) mice were assigned to the normal control group (six mice) and EAU model group (thirty-nine mice).The mice were immunized subcutaneously at 6 spots on the footpads,tail base,and flank with emulsion containing human interphotoreceptor retinoid binding protein1-20 (IRBP1-20) emulsified in complete Freund's adjuvant.After immunization,the mice were examined for clinical signs of EAU by using a Genesis-D camera.The changes of histopathology were compared by hematoxylin and eosin staining.Mouse lymphocytes were isolated and purified from the spleens of IRBP1-20-immunized or normal B6 mice by using a γδ T-cell isolation kit.Flow cytometry was used to detect the changes of intracellular expression of interleukin-17A (IL-17A),and then transferred the activated γδ T cells into EAU models to analyze the changes of clinical signs and histopathology of EAU.Experimental study program as well as the use and feeding of the animals were authorized by the Animal Management and Use Committee of Shandong Traditional Chinese Medicine University.Results The inflammatory symptoms in mouse eyes appeared on day 12 after modeling.The initial changes were fundal blood vessel thickening and minimal inflammatory cell infiltration.Then,multifocal chorioretinal lesions,serious vasculitis and linear lesions were observed on days 16-20,along with abundant lymphocyte infiltration in the vitreous and retinal disorganization.The inflammation symptom scores and the pathological inflammation scores at different time points after modeling had statistically significant differences (F =51.399,P =0.000;F =47.342,P =0.000).The inflammatory symptoms in the eyes began to abate from day 28 onwards.The number of γδ T cells was obviously increased during the inflammation phase of EAU at day 16-20 after modeling,with the number of γδ T cells was (5.67 ±-0.49) % and (5.78 ±±0.55) %,respectively,which was significantly higher than (1.53 ± 0.14) % before modeling,with significant differences between them (both at P<0.05),meanwhile CD69 levels and the integrin lymphocyte function-associated antigen-1 (LFA-1) and secreted IL-17A were elavated.The secretion level of IL-17A was (13.40±0.50)% and (17.80±2.37)% on day 16 and day 20 after modeling,respectively,which was significantly higher than (1.53 ± 0.19) % before modeling,with significant differences between them (P =0.000,0.001).The activated γδ T cells were transferred into EAU model,the inflammation symptom scores were 1.00 (1.00,2.00) after activated γδ T cells were transferred into EAU model,which was significantly higher than 0.75 (0.05,1.00) of the untransferred group (Z =27.00,P =0.03),and the symptoms of EAU were aggravated.Conclusions The proportion of γδ T cells reaches peak in inflammation of EAU,and the cells are activated.The activated γδ T cells in the EAU model play a immune regulation role by secreting IL-17A.
6.Research progress in the mechanism of selenium supplement therapy for thyroid associated ophthalmopathy
Chinese Journal of Experimental Ophthalmology 2017;35(9):857-861
Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune-inflammatory disorder,ranking top among the orbital diseases with highest incidences.TAO is characterized by a complex pathogenesis,including glycosaminoglycan and hyaluronic acid deposition,fibrosis of extraocular muscle and adipose degeneration of ocular tissue.The physical manifestations of the disease include periorbital edema,double vision,ophthalmoptosis,ocular dryness,eyelid retraction and on occasion vision loss secondary to optic nerve compression.Selenium evolves in the diversified pathogenesis of TAO.Although the therapeutic effects for TAO of selenium have already been proven,some problems appear to be no clear among the clinicians,such as its optimum dose,duration of the treatment,and safety to date,etc.Nowadays,the mechanism of selenium supplementation in TAO treatment includes neutralization of reactive oxygen,inhibition of HLA-DR expression,inhibition of secretion of TSHR-Ab and TPO-Ab.The aim of the review was to summarize the studies of selenium supplementation theray for TAO.
7.A randomized controlled clinical study on the combination of preservative-free sodium hyaluronate and fluorometholone eyedrops for cataract with dry-eye
Zhe, YIN ; Rui, YIN ; Yuanbin, LI
Chinese Journal of Experimental Ophthalmology 2017;35(9):843-847
Background Cataract with preexisted dry eye is a common eye disease.It is speculated that preservative-free artificial tears can inhibit inflammatory procedure,prevent postoperative eye infections and reduce dry eye symptoms.However,relevant literature is rare up to now.Objective This study was to evaluate and compare the therapeutic effects between preservative-free or preservative sodium hyaluronate combined with fluorometholone eyedrops for cataract with dry-eye.Methods A randomized controlled single-blind clinical study was performed.Sixty patients with dry-eye syndrome who was going to receive surgery for cataract removal were enrolled in Yuhuangding Hospital from January to December 2015 under the informed consent.The patients were randomly divided into the test group and control group.Preservative-free or preservative 0.1% sodium hyaluronate combined with 0.1% fluorometholone eye drops were topically administered in the eyes of the test group and control group,respectively.Ocular Surface Disease Index (OSDI) score,breakup time of tearfilm (BUT),Schirmer Ⅰ test (S I t),corneal fluorescein staining,impression cytology,goblet cell density and the concentrations of interleukin (IL)-1β,tumor necrosis factor (TNF)-α,catalase (CAT),superoxide dismutase 2 (SOD2) in tears were evaluated and compared.Results There were significant differences in gender,ages,OSDI scores,BUT,S I t value,corneal fluorescein staining scores,impression cytology findings,and goblet cell density between the two groups (all at P>0.05).OSDI,corneal fluorescein staining scores and imprint cellular level were evidently reduced,and BUT,S I t values and goblet cell density were significantly increased 1 month and 2 months after operation in comparison with the baseline values in the test group (F =13.058,8.027,3.755,21.652,70.962,92.354,all at P < 0.05).The concentrations of IL-1β and TNF-α in tears of the test group were significantly lower,and CAT and SOD2 in the tears of the test group were significantly higher than those in the control group 1 month and 2 months after operation (F=18.731,9.070,15.357,351.359,all at P>0.05).Conclusions 0.1% preservative-free sodium hyaluronate combined with 0.1% fluorometholone eyedrops can relieve the symptoms and signs of dry-eyes following cataract surgery by playing antiinflammatory and antioxidant effects.
8.Promoting effects of insulin-like growth factor-1 on proliferation of orbital fibroblasts derived from thyroid associated ophthalmopathy
Jialing, DAI ; Weimin, HE ; Mengqi, LUO
Chinese Journal of Experimental Ophthalmology 2017;35(9):805-810
Background Thyroid associated ophthalmopathy (TAO) is an autoimmune disease.Current research on the pathogenesis focuses on common autoantigen.Insulin-like growth factor-1 receptor (IGF-1R) is necessary for the function of IGF-1,also IGF-1 plays an important role in signaling pathway of thyroid stimulating hormone receptor (TSHR).Objective This study was to investigate the effects of IGF-1 on the proliferation,expression of IGF-1R and TSHR on cultured orbital fibroblasts (OFs) derived from TAO.Methods Human orbital tissue was obtained from 17 TAO patients who received orbital adipectomy and 4 normal controls who received cosmetic surgery in West China Hospital from March 2016 to June 2016.OFs were cultured by explant culture with DMEM/F12 containing 5% fetal bovine serum and identified by immunochemistry.The OFs were treated with different concentrations of IGF-1.IGF-1 at different concentrations (0,50,100,125 μg/L) was added into the medium,respectively,and the proliferation of the cells (absorbancy) was detected by MTS.The percentages of IGF-1R and TSHR expressions in the cells were assayed by flow cytometry.Results Cultured cells appeared to be spindle-like in shape and grew well with abundant cytoplasm.The characteristics of the cells derived from TAO patients were consistant with normal ones.The cells showed the positive response for vimentin and absent respose for desmin,S-100,myoglobin and cytokeratin.The proliferative values of OFs were gradually elevated with the increase of IGF-I dose in both TAO group and normal group (Fgroup =219.639,P<0.001;F ion =17.752,P<0.001) with the optimal effects in 100 μg/L IGF-1.The expression levels of IGF-1R in the OFs were (0.009 1 ±0.008 7)%,(0.095 3±0.023 3) %,(0.083 7±0.022 7) % and (0.070 9 ± 0.024 1) % in the TAO group,and those in the normal group were (0.0023± 0.0006)%,(0.0093±0.0012)%,(0.0073±0.0015)% and (0.0083±0.0012)% after treatment of 50,100,125 μg/L IGF-1.The expression levels of IGF-1 R were significantly higher after treatment of 50,100 and 125 μtg/L IGF-1 than those treatment of 0 μg/L IGF-1 in both TAO group and normal group,and the expression levels of IGF-1R in the OFs were significantly increased in the TAO group compared with the normal group (all at P<0.05).No statistical difference was seen in the TSHR expression between the TAO group and normal group after treatment of 0,50,100 and 125 μg/L IGF-1 (Fgroup =0.133,P > 0.05;F ion =0.004,P > 0.05).Conclusions IGF-1 can promote the proliferation of OFs and up-regulate the expression of IGF-1R in OFs.However,IGF-1 dose not play a regulating effect on the expression of TSHR in OFs.
9.A comparative study of visual quality between implantable collamer lens implantation and femtosecond LASIK for myopia
Ruina, WANG ; Hongliang, GUO ; Ting, MA ; Houcheng, LIANG ; Tan, LONG
Chinese Journal of Experimental Ophthalmology 2017;35(9):833-837
Background The incidence of myopia is gradually increasing,and how to choose a better corrective method of myopia for the best visual demand is very important.Objective This study was to compare visual quality of implantable collamer lens (ICL) implantation with femtosecond laser in situ keratomileusis (FSLASIK) for moderate and high myopia using double-pass optical quality analysis system (OQAS).Methods A non-randomized controlled clinical trail was performed.Fifty-two eyes with-4.00 to-9.00 D of 26 consecutive patients were included in NO.1 Hospital of Xi'an from January 2015 to January 2016.Twenty-four eyes of 12 patients with the corneal thickness <500 μm received ICL implantation as ICL group and 28 eyes of 14 patients which corneal thickness was ≥500 μm underwent FS-LASIK surgery as FS-LASIK group.The demography was matched between the two groups (all at P>0.05).All the patients were followed-up for 3 months after surgery.The preoperative best corrected distance visual acuity (BCDVA),spherical equivalent (SE),postoperative uncorrected distance visual acuity (UCDVA),BCDVA and SE were examined and compared between two groups.The parameters from OQAS were evaluated and intergrouply compared,including the objective scattering inders (OSI),modulation transfer function (MTF) cut off frequency,Strehl ratio and OQAS values under the contrast of 100%,20% and 9% (OV100,OV20,OV9).Results The postoperative BCDVA was not significantly different from preoperative UCDVA in both ICL group and FS-LASIK group (-0.04±t0.10 vs.0.05±0.12;-0.07±0.12 vs.0.00±0.12) (t=3.128,2.358,both at P>0.05).No statistically significant differnces were found in SE,UCDVA and BCDVA after operation between ICL group and FS-LASIK group (t =1.292,0.900,-0.653,all at P>0.05).OQAS examination showed that MTF cut off,OSI,Strehl ratio,OV100 were not significantly different after operation between ICL group and FS-LASIK group (t=-2.032,-1.440,-0.224,all at P>0.05).The postoperative OV20 and OV9 were 0.82±0.14 and 0.80±0.21 in the ICL group,which were significantly higher than those in the FS-LASIK group(0.59±0.15 and 0.47±0.13) (t =4.105,4.702,both at P<0.05).Conclusions Both ICL implantation and FS-LASIK provide good optical and visual quality for moderate to high myopic eyes,and ICL appears to have a better visual quality in comparison with FS-LASIK under the contrasts of 20% and 9%.
10.Eyelid examination for Demodex infestation
Liping, LIN ; Haisu, YI ; Jiahao, SITU ; Lingyi, LIANG ; Xinguo, DENG ; Kaili, WU
Chinese Journal of Experimental Ophthalmology 2017;35(9):829-832
Background Blepharitis caused by Demodex infestation is very common in clinical practice.There are various methods mentioned in the study of Demodex infestation in China,but a unified introduction and evaluation of the operating procedures is lacked.A quick and accurate clinical diagnostic method for Demodex infestation needs to be further studied.Objective This study aimed to establish operation procedures for the clinical examination of eyelid Demodex infestation,which were applied to evaluate the conditions of eyelid Demodex infestation in ocular patients with discomfort.Methods One thousand and fifty-two patients with eye dryness,eye itchiness or other symptoms were selected for slit lamp examination and photographing of the eyelid margin area.Three eyelashes with associated scurf from each superior eyelid were plucked out for examination of Demodex under the microscope.Positive findings included observation of Demodex mites or eggs.Their amounts were recorded individually for all eyelash samples.Results A procedure for observing,recording and reporting eyelid Demodex infestations in patients was successfully established.By using this procedure,1 052 patients were investigated for the examination of Demodex infestations.Demodex mites or eggs were found in 582 cases (55.3%).The positive rate of Demodex infestation increased with age,and the population over 60 years group had the highest positive rate,showing a significant difference among the different age groups (x2=10.547,P=0.001).There was no significant difference in positive rate between male patients and female patients (P =0.352).The test turnaround time (TAT) for one examination was (11.4±5.2) seconds.Conclusions The operational procedure for examining the palpebral margin Demodex infestation by the slit-lamp,optical microscope,photographing and laboratory reports is established.It is simple and quick in the appliation for the clinical diagnosis of eyelid Demodex infestation.