The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal vir...The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the cornea.One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea.After the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the eye.The virus may remain dormant for extended periods.Periodic reactivation of the virus can occur,leading to recurrent episodes of HSK.Factors triggering reactivation include stress,illness,immunosuppression,or trauma.Recurrent episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial disease.The severity and frequency of recurrences vary among individuals.Severe cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme cases.The cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual impairment.The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization.Antiviral medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for prophylaxis.The immune response to the virus can contribute to corneal damage.Inflammation,caused by the body's attempt to control the infection,may inadvertently harm the corneal tissues.Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation.In summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.展开更多
AIM:To explore whether unilateral herpes simplex keratitis(HSK)can cause morphological changes of bilateral meibomian glands(MGs)based on artificial intelligence(AI)analytical system.METHODS:In the retrospective study...AIM:To explore whether unilateral herpes simplex keratitis(HSK)can cause morphological changes of bilateral meibomian glands(MGs)based on artificial intelligence(AI)analytical system.METHODS:In the retrospective study,29 patients with unilateral HSK and 29 participants matched in terms of age and sex were included as control group.Meibographic images of the upper eyelid using Keratograph 5M and assessed ocular surface parameters including tear meniscus height and tear break-up time.MG density and vagueness values were automatically analyzed and calculated using an AI analytical system.We compared the differences between the affected and the contralateral unaffected eyes in HSK patients,and the normal control eyes.We employed either the paired t-test or the Wilcoxon signed-rank test to compare significant difference between the affected and unaffected eyes in HSK patients or between the HSK group and control group.RESULTS:The MG density was 0.19±0.09 in the HSKaffected eye and 0.18±0.07 in contralateral unaffected eye,which had no significant difference(P=0.616).The MG density between the affected eye with HSK and the normal control group was statistically significant(P=0.028).There was a significant difference in MG density between the contralateral unaffected eye and the normal control group(P=0.012).However,no significant difference in vagueness value was observed between the eye with HSK and the control group or between HSK eye and contralateral eye.CONCLUSION:The MG density between the HSKaffected eye and the contralateral unaffected eye don’t significantly differ,whereas there is a significant decrease in the HSK group compared to that of the normal participants.Unilateral HSV keratitis may suffer from bilateral changes of MG morphology indicating bilateral dry eye.Therefore,the fellow eye of patients with unilateral HSK should be considered a potential case of MG dysfunction,necessitating early treatment for bilateral dry eye in the clinic.展开更多
HSV-DNA of seven corneal lesions suspected with herpessimplex keratitis (HSK) and nine normal human donor corneas weredetected by PCR,Five out of seven diseased corneas showed positiveresults,and the other two disease...HSV-DNA of seven corneal lesions suspected with herpessimplex keratitis (HSK) and nine normal human donor corneas weredetected by PCR,Five out of seven diseased corneas showed positiveresults,and the other two diseased corneas and nine.normal corneasnegative.The results suggest the PCR may be useful as a rapid andsensitive method for diagnosing HSK.Eye Science 1993;9:126-128.展开更多
Objective:To explore the effects of integrated traditional Chinese and western Medicine on the vision recovery and serum trace elements in patients with herpes simplex keratitis.Methods:A total of 86 cases of HSK pati...Objective:To explore the effects of integrated traditional Chinese and western Medicine on the vision recovery and serum trace elements in patients with herpes simplex keratitis.Methods:A total of 86 cases of HSK patients admitted in Baogang Hospital of Inner Mongolia from January 2015 to October 2016 were selected and divided randomly into the observation group(n=43)and the control group(n=43)according to the random number table.The control group was treated with ganciclovir eye drops and chondroitin sulfate eye drops,and the observation group was treated with Qinggan Mingmu Decoction on the basis of the control group.The 2 groups were treated for 4 weeks continuously.The clinical efficacy was compared between two groups.The vision recovery,serum trace elements and tear immune factor levels were also compared between two groups before and after treatment.Results:After treatment,the effective rate of treatment in the observation group was significantly higher than that in the control group(p<0.05);in the observation group of patients,visual analogue scale(VAS)score and visual acuity after treatment were obviously higher than those before treatment,and also remarkably higher than those in the control group of patients(p<0.05);after treatment,the levels of Fe,Ca and Cu ions in the observation group were significantly lower than those in the control group and before treatment(p<0.05);after treatment,the level of zinc ions in the serum in the observation group was significantly higher than that before treatment and in the control group(p<0.05);after treatment,the levels of tear IgA,IgG and C3 in the observation group were prominently higher than those before treatment and in the control group(p<0.05).Conclusions:In the treatment of HSK,integrated traditional Chinese and western medicine can promote effectively the vision recovery,regulate the level of trace elements in the serum and enhance the level of tear immune factors,with the clinical efficacy better than the treatment of western medicine alone.展开更多
Purpose:To elucidate the role of adhesion molecules in the pathogenesis of herpes simplex keratitis. Methods:Fifty female Balb/c mice (4-6 weeks old, 14-22 g weight) were divided into two groups randomly. Forty were i...Purpose:To elucidate the role of adhesion molecules in the pathogenesis of herpes simplex keratitis. Methods:Fifty female Balb/c mice (4-6 weeks old, 14-22 g weight) were divided into two groups randomly. Forty were infected by herpes simplex virus and the other 10 were used as normal controls.All mice were fed under the same conditions.Corneas of these mice were collected for immunohistochemical testing on day 14 and 21 after infection. Results:ICAM-1 was mainly expressed in the basal cells of the corneal epithelia and vascular endothelia of the infected mice. A substantial amount of VCAM-1 was also expressed in the corneal vascular endothelial cells of infected mice,and was also found in inflammatory cells in the epithelial and stromal layers of the corneas. Conclusion:Adhesion molecules ICAM-1 and VCAM-1 were involved in the progression of herpex simplex keratitis.They may accelerate the progress of inflammation by mediating the extravsation of inflammatory cells from vessels into the infected sites.展开更多
AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1(HSV-1) glycoprotein C(g C) and glycoprotein D(g D) will achieve better protective effect against herpes simplex keratitis(HSK) than DNA ...AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1(HSV-1) glycoprotein C(g C) and glycoprotein D(g D) will achieve better protective effect against herpes simplex keratitis(HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined g D(g D.g C) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells(NK),when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.展开更多
This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear ce...This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells(PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment(inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1(HSV-1) infection resulted in significantly elevated peripheral levels of IL-1β in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1β in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1β may have implications for HSV-1 viral clearance in active and inactive HSK patients.展开更多
Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were o...Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p < 0.05). ADV DNA was detected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.展开更多
Background:Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1),which has high recurrent rate and incidence of severe vision loss,is the leading cause of infectious blindness in the world.The a...Background:Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1),which has high recurrent rate and incidence of severe vision loss,is the leading cause of infectious blindness in the world.The aim was to explore the clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK.Methods:A multicenter,prospective,randomized,single-blind,and controlled clinical trial was conducted from April 2010 to June 2013.One hundred seventy-three patients (173 eyes involved) who were diagnosed as recurrent HSK definitely,including stromal keratitis and corneal endotheliitis,were divided into three groups randomly:negative control (placebo) group was topically administered with 0.15% GCV ophthalmic gel,4 times per day and 0.1% fluorometholone eye drops,3 times per day until resolution of HSK; positive control acyclovir (ACV) group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks.The symptoms and signs were evaluated before and after the therapy 1^st week,2^nd week and then followed up every 2 weeks until recovery.Furthermore,we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time,recurrent rate and adverse reactions.Results:One hundred and seventy-three patients were followed up 7-48 months (mean 32.1 ± 12.3 months),but 34 patients were failed to follow-up.The cure time was 12.1± 4.3,11.9 ± 4.0 weeks in negative control (placebo) group and positive control ACV group respectively (P =0.991),which was longer than that in test GCV group (8.6 ± 2.8 weeks) and there was a significant difference between test GCV group and negative control (placebo) group or positive control ACV group (P =0.000).Furthermore,the recurrent rate was higher in negative control (placebo) group (47.3%) than that in positive control group ACV (26.7%) and test GCV group (17.2%),and there was a great significant difference among the three groups (P =0.007),but there was no significant difference between positive control ACV group and test GCV group (P =0.358).In addition,there was no obvious adverse reaction expect neutropenia (only one patient in test GCV group).Conclusion:Short-term oral GCV could cure recurrent HSK and endotheliitis,shorten the course,reduce recurrent rate of HSK and have confirmed safety.展开更多
AIM: To describe and compare corneal sensation and morphological changes of sub-basal corneal nerves by in vivo laser scanning confocal microscopy(LSCM) in herpes simplex virus(HSV) keratitis/uveitis and contralateral...AIM: To describe and compare corneal sensation and morphological changes of sub-basal corneal nerves by in vivo laser scanning confocal microscopy(LSCM) in herpes simplex virus(HSV) keratitis/uveitis and contralateral, clinically unaffected eyes. METHODS: A prospective clinical study included 30 HSV eyes and 30 contralateral eyes of 30 patients, diagnosed with unilateral HSV keratitis/uveitis. Both eyes underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM of the central cornea, using the Heidelberg Retina Tomograph III Rostock Cornea Module. After 6 mo, the same examination of the HSV affected and contralateral, clinically unaffected eyes was performed.RESULTS: HSV eyes, as compared to contralateral eyes, demonstrated a significant decrease in mean corneal sensation(3.1±1.6 vs 5.3±0.8 cm), total nerve fibres number(5.7±4.4 vs 15.1±5.4), nerve branches(3.4±3.0 vs 8.4±4.7), main nerve trunks(2.3±1.6 vs 5.8±2.2), and nerve fibres density(7.5±5.6 vs 18.1±5.3 mm/mm2, P<0.05). There was no significant difference between keratitis and uveitis eyes in mean corneal sensation and nerve fibres parameters. After 6 mo, corneal sensation and sub-basal nerve fibres parameters were increased significantly, but did not reach the parameters of contralateral, clinically unaffected eyes.CONCLUSION: Corneal aesthesiometry and LSCM in HSV affected eyes reveals a significant decrease of corneal sensation and sub-basal nerve fibres which recovers at6 mo but does not reach the normal level.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,...AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,HeLa,and BV2 cells were infected with HSV1[HSV1f strain,HSV1f;HSV-1-H129 with green fluorescent protein(GFP)knock-in,HSV1g].Pre-or post-infection,SAL at various concentrations was added to the culture medium for 24 h.GFP fluorescence in HSV1g or plaque formation by HSV1f were examined.The effects of heat-treated SAL,precooled acetone-precipitated SAL,and SAL subjected to ultrafiltration(100 kDa)were evaluated.The effects of other bacterial components and lysates on HSV1 infection were also tested,including lipoteichoic acid(LTA),peptidoglycan(PGN),staphylococcal protein A(SPA),andα-hemolysin from S.aureus(α-toxin)as well as lysates from a wild-type S.aureus strain,S.epidermidis,and Escherichia coli(W-SAL,SEL,and ECL,respectively).In addition,SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis,followed by in vivo observations.RESULTS:The cytopathic effect,plaque formation(HSV1f),and GFP expression(HSV1g)in infected cells were inhibited by SAL in a dose-dependent manner.The active component of SAL(≥100 kDa)was heat-sensitive and retained activity after acetone precipitation.In HSV1ginfected cells,treatment with LTA-sa,α-toxin,PGN-sa,or SPA did not inhibit GFP expression.SAL,W-SAL,and SEL(but not ECL)decreased GFP expression.In mice with HSV1 keratitis,SAL reduced corneal lesions by 71%.CONCLUSION:The results of this study demonstrate that SAL can be used to inhibit HSV1 infection,particularly keratitis.Further studies are needed to determine the active components and mechanism underlying the effects of SAL.展开更多
文摘The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the cornea.One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea.After the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the eye.The virus may remain dormant for extended periods.Periodic reactivation of the virus can occur,leading to recurrent episodes of HSK.Factors triggering reactivation include stress,illness,immunosuppression,or trauma.Recurrent episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial disease.The severity and frequency of recurrences vary among individuals.Severe cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme cases.The cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual impairment.The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization.Antiviral medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for prophylaxis.The immune response to the virus can contribute to corneal damage.Inflammation,caused by the body's attempt to control the infection,may inadvertently harm the corneal tissues.Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation.In summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.
基金Supported by Zhejiang Provincial Medical and Health Science Technology Program,Health Commission of Zhejiang Province(No.2022PY074)Science and Technology Program of Wenzhou City(No.Y2020335).
文摘AIM:To explore whether unilateral herpes simplex keratitis(HSK)can cause morphological changes of bilateral meibomian glands(MGs)based on artificial intelligence(AI)analytical system.METHODS:In the retrospective study,29 patients with unilateral HSK and 29 participants matched in terms of age and sex were included as control group.Meibographic images of the upper eyelid using Keratograph 5M and assessed ocular surface parameters including tear meniscus height and tear break-up time.MG density and vagueness values were automatically analyzed and calculated using an AI analytical system.We compared the differences between the affected and the contralateral unaffected eyes in HSK patients,and the normal control eyes.We employed either the paired t-test or the Wilcoxon signed-rank test to compare significant difference between the affected and unaffected eyes in HSK patients or between the HSK group and control group.RESULTS:The MG density was 0.19±0.09 in the HSKaffected eye and 0.18±0.07 in contralateral unaffected eye,which had no significant difference(P=0.616).The MG density between the affected eye with HSK and the normal control group was statistically significant(P=0.028).There was a significant difference in MG density between the contralateral unaffected eye and the normal control group(P=0.012).However,no significant difference in vagueness value was observed between the eye with HSK and the control group or between HSK eye and contralateral eye.CONCLUSION:The MG density between the HSKaffected eye and the contralateral unaffected eye don’t significantly differ,whereas there is a significant decrease in the HSK group compared to that of the normal participants.Unilateral HSV keratitis may suffer from bilateral changes of MG morphology indicating bilateral dry eye.Therefore,the fellow eye of patients with unilateral HSK should be considered a potential case of MG dysfunction,necessitating early treatment for bilateral dry eye in the clinic.
文摘HSV-DNA of seven corneal lesions suspected with herpessimplex keratitis (HSK) and nine normal human donor corneas weredetected by PCR,Five out of seven diseased corneas showed positiveresults,and the other two diseased corneas and nine.normal corneasnegative.The results suggest the PCR may be useful as a rapid andsensitive method for diagnosing HSK.Eye Science 1993;9:126-128.
文摘Objective:To explore the effects of integrated traditional Chinese and western Medicine on the vision recovery and serum trace elements in patients with herpes simplex keratitis.Methods:A total of 86 cases of HSK patients admitted in Baogang Hospital of Inner Mongolia from January 2015 to October 2016 were selected and divided randomly into the observation group(n=43)and the control group(n=43)according to the random number table.The control group was treated with ganciclovir eye drops and chondroitin sulfate eye drops,and the observation group was treated with Qinggan Mingmu Decoction on the basis of the control group.The 2 groups were treated for 4 weeks continuously.The clinical efficacy was compared between two groups.The vision recovery,serum trace elements and tear immune factor levels were also compared between two groups before and after treatment.Results:After treatment,the effective rate of treatment in the observation group was significantly higher than that in the control group(p<0.05);in the observation group of patients,visual analogue scale(VAS)score and visual acuity after treatment were obviously higher than those before treatment,and also remarkably higher than those in the control group of patients(p<0.05);after treatment,the levels of Fe,Ca and Cu ions in the observation group were significantly lower than those in the control group and before treatment(p<0.05);after treatment,the level of zinc ions in the serum in the observation group was significantly higher than that before treatment and in the control group(p<0.05);after treatment,the levels of tear IgA,IgG and C3 in the observation group were prominently higher than those before treatment and in the control group(p<0.05).Conclusions:In the treatment of HSK,integrated traditional Chinese and western medicine can promote effectively the vision recovery,regulate the level of trace elements in the serum and enhance the level of tear immune factors,with the clinical efficacy better than the treatment of western medicine alone.
文摘Purpose:To elucidate the role of adhesion molecules in the pathogenesis of herpes simplex keratitis. Methods:Fifty female Balb/c mice (4-6 weeks old, 14-22 g weight) were divided into two groups randomly. Forty were infected by herpes simplex virus and the other 10 were used as normal controls.All mice were fed under the same conditions.Corneas of these mice were collected for immunohistochemical testing on day 14 and 21 after infection. Results:ICAM-1 was mainly expressed in the basal cells of the corneal epithelia and vascular endothelia of the infected mice. A substantial amount of VCAM-1 was also expressed in the corneal vascular endothelial cells of infected mice,and was also found in inflammatory cells in the epithelial and stromal layers of the corneas. Conclusion:Adhesion molecules ICAM-1 and VCAM-1 were involved in the progression of herpex simplex keratitis.They may accelerate the progress of inflammation by mediating the extravsation of inflammatory cells from vessels into the infected sites.
基金Supported by Natural Science Foundation of Jiangsu Province (No.BK20141346)Nanjing Science and Technology Development Plan (No.201402001)
文摘AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1(HSV-1) glycoprotein C(g C) and glycoprotein D(g D) will achieve better protective effect against herpes simplex keratitis(HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined g D(g D.g C) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells(NK),when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.
基金Supported by the Health Research Board and the Royal Victoria Eye and Ear Hospital Research Foundation through the Medical Research Charities Group(No.1409)
文摘This study sought to identify potential therapeutic targets in herpes simplex keratitis(HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells(PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment(inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1(HSV-1) infection resulted in significantly elevated peripheral levels of IL-1β in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1β in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1β may have implications for HSV-1 viral clearance in active and inactive HSK patients.
文摘Purpose: To compare the clinical and molecular diagnoses of Herpes Simplex Keratitis (HSK). Materials and Methods: Conjunctival swabs (after fluorescein and anaesthetic wash out) and detailed questionnaire data were obtained from 146 participants. Corneal rims and conjunctival epithelial cells were infected with Herpes Simplex Virus (HSV) type 1 or HSV2 and supernatant collected. HSV1;HSV2;Varicella Zoster Virus (VZV) and Adenovirus (ADV) DNA was assessed using two real time Polymerase Chain Reaction (PCR) methods. Results: Of the 146 participants recruited, 54 were clinically diagnosed with typical epithelial lesions and 38 with atypical epithelial lesions, 17 with old inactive HSK and 37 healthy volunteers. HSV1 DNA was detected in 28 (30%) of the 92 participants with clinically suspect HSK. Patients who presented with typical epithelial lesions had a higher positive rate (46%) than those who presented with atypical type lesions (8%), when using primers against the Glycoprotein (Gp) G region of the virus. When the same samples were retested with primers against the GpB region, the positive rate for the typical and atypical cases increased to 52% and 11% respectively. Antiviral use at the time of sampling reduced the rate of PCR positivity by 20% (p < 0.05). ADV DNA was detected in 6% of the typical cases and 8% of the atypical cases. All control participants with no history of HSK were negative for HSV1 DNA. Sample quantity was confirmed by testing for housekeeping control genes, beta-actin and beta-2 macroglobulin. PCR results from in vitro control investigations of HSV1 and 2 infected corneal rims and conjunctival epithelial cells were 100% positive for infected and 100% negative for uninfected samples when assessed using both PCR methods. Conclusions: Clinical diagnosis of typical HSK is not always confirmed by PCR. Concomitant use of an antiviral reduces levels of PCR positivity. Given this and the findings that other ocular surface pathogens may mimic HSK pathology, and that choice of gene amplification region can also affect accurate detection of HSV1 by PCR, we propose the use of a multiplex assay. This would perform PCR using primers spanning a number of different regions within one gene and would also target a number of different viral genes to ensure potentially different HSV1 viral strains or other viruses do not affect the test and lead to disagreements between the clinical and molecular diagnosis of HSK. From these findings, this paper proposes a clinical supportive algorithmic guide to manage such disagreements.
文摘Background:Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1),which has high recurrent rate and incidence of severe vision loss,is the leading cause of infectious blindness in the world.The aim was to explore the clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK.Methods:A multicenter,prospective,randomized,single-blind,and controlled clinical trial was conducted from April 2010 to June 2013.One hundred seventy-three patients (173 eyes involved) who were diagnosed as recurrent HSK definitely,including stromal keratitis and corneal endotheliitis,were divided into three groups randomly:negative control (placebo) group was topically administered with 0.15% GCV ophthalmic gel,4 times per day and 0.1% fluorometholone eye drops,3 times per day until resolution of HSK; positive control acyclovir (ACV) group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks.The symptoms and signs were evaluated before and after the therapy 1^st week,2^nd week and then followed up every 2 weeks until recovery.Furthermore,we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time,recurrent rate and adverse reactions.Results:One hundred and seventy-three patients were followed up 7-48 months (mean 32.1 ± 12.3 months),but 34 patients were failed to follow-up.The cure time was 12.1± 4.3,11.9 ± 4.0 weeks in negative control (placebo) group and positive control ACV group respectively (P =0.991),which was longer than that in test GCV group (8.6 ± 2.8 weeks) and there was a significant difference between test GCV group and negative control (placebo) group or positive control ACV group (P =0.000).Furthermore,the recurrent rate was higher in negative control (placebo) group (47.3%) than that in positive control group ACV (26.7%) and test GCV group (17.2%),and there was a great significant difference among the three groups (P =0.007),but there was no significant difference between positive control ACV group and test GCV group (P =0.358).In addition,there was no obvious adverse reaction expect neutropenia (only one patient in test GCV group).Conclusion:Short-term oral GCV could cure recurrent HSK and endotheliitis,shorten the course,reduce recurrent rate of HSK and have confirmed safety.
文摘AIM: To describe and compare corneal sensation and morphological changes of sub-basal corneal nerves by in vivo laser scanning confocal microscopy(LSCM) in herpes simplex virus(HSV) keratitis/uveitis and contralateral, clinically unaffected eyes. METHODS: A prospective clinical study included 30 HSV eyes and 30 contralateral eyes of 30 patients, diagnosed with unilateral HSV keratitis/uveitis. Both eyes underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM of the central cornea, using the Heidelberg Retina Tomograph III Rostock Cornea Module. After 6 mo, the same examination of the HSV affected and contralateral, clinically unaffected eyes was performed.RESULTS: HSV eyes, as compared to contralateral eyes, demonstrated a significant decrease in mean corneal sensation(3.1±1.6 vs 5.3±0.8 cm), total nerve fibres number(5.7±4.4 vs 15.1±5.4), nerve branches(3.4±3.0 vs 8.4±4.7), main nerve trunks(2.3±1.6 vs 5.8±2.2), and nerve fibres density(7.5±5.6 vs 18.1±5.3 mm/mm2, P<0.05). There was no significant difference between keratitis and uveitis eyes in mean corneal sensation and nerve fibres parameters. After 6 mo, corneal sensation and sub-basal nerve fibres parameters were increased significantly, but did not reach the parameters of contralateral, clinically unaffected eyes.CONCLUSION: Corneal aesthesiometry and LSCM in HSV affected eyes reveals a significant decrease of corneal sensation and sub-basal nerve fibres which recovers at6 mo but does not reach the normal level.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
基金the National Natural Science Foundation of China(No.81770896,No.81970848)the Guangzhou Science Technology and Innovation Commission(No.201607020011)。
文摘AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,HeLa,and BV2 cells were infected with HSV1[HSV1f strain,HSV1f;HSV-1-H129 with green fluorescent protein(GFP)knock-in,HSV1g].Pre-or post-infection,SAL at various concentrations was added to the culture medium for 24 h.GFP fluorescence in HSV1g or plaque formation by HSV1f were examined.The effects of heat-treated SAL,precooled acetone-precipitated SAL,and SAL subjected to ultrafiltration(100 kDa)were evaluated.The effects of other bacterial components and lysates on HSV1 infection were also tested,including lipoteichoic acid(LTA),peptidoglycan(PGN),staphylococcal protein A(SPA),andα-hemolysin from S.aureus(α-toxin)as well as lysates from a wild-type S.aureus strain,S.epidermidis,and Escherichia coli(W-SAL,SEL,and ECL,respectively).In addition,SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis,followed by in vivo observations.RESULTS:The cytopathic effect,plaque formation(HSV1f),and GFP expression(HSV1g)in infected cells were inhibited by SAL in a dose-dependent manner.The active component of SAL(≥100 kDa)was heat-sensitive and retained activity after acetone precipitation.In HSV1ginfected cells,treatment with LTA-sa,α-toxin,PGN-sa,or SPA did not inhibit GFP expression.SAL,W-SAL,and SEL(but not ECL)decreased GFP expression.In mice with HSV1 keratitis,SAL reduced corneal lesions by 71%.CONCLUSION:The results of this study demonstrate that SAL can be used to inhibit HSV1 infection,particularly keratitis.Further studies are needed to determine the active components and mechanism underlying the effects of SAL.