Growth hormone-releasing hormone receptor signaling in experimental ocular inflammation and neuroprotection

Both inflammation and anti-inflammation are involved in the protection of retinal cells.Antagonists of the hypothalamic growth hormone-releasing hormone receptor(GHRHR)have been shown to possess potent anti-inflammatory properties in experimental disease models of various organs,some with systemic complications.Such effects are also found in ocular inflammatory and neurologic injury studies.In experimental models of mice and rats,both growth hormone-releasing hormone receptor agonists and antagonists may alleviate death of ocular neural cells under certain experimental conditions.This review explores the properties of growth hormone-releasing hormone receptor agonists and antagonists that lead to its protection against inflammatory responses induced by extrinsic agents or neurologic injures in ocular animal models.

Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases:a two-sample Mendelian randomization study

AIM:To investigate the causal effect of inflammatory bowel disease(IBD)on ocular inflammation using Mendelian randomization(MR)analysis.METHODS:Genetic instruments associated with inflammatory bowel disease(IBD),ulcerative colitis(UC),and Crohn’s disease(CD)were derived from the largest genome-wide association studies(GWAS)published to date.The FinnGen research project was utilized to identify genetic risk variants associated with conjunctivitis,keratitis,iridocyclitis,chorioretinitis,episcleritis,and optic neuritis.All participants were of European ancestry.Three methods which included inverse variance weighting(IVW),weighted median(WM),and MR-Egger regression were performed to estimate the causal association in this study.IVW took the inverse variance of each study as the weight to calculate the weighted average of effect sizes,to summarize the effect sizes of multiple independent studies,which could provide the most precise estimated results.IVW was used as the primary outcome,while WM and MR-Egger were used to improve the estimation of IVW.RESULTS:A nominal causal effect of genetically predicted IBD on risk of non-infectious conjunctivitis,keratitis,iridocyclitis,and optic neuritis,but not on chorioretinitis or episcleritis.After Bonferroni correction,the results showed that genetically predicted UC was significantly associated with an increased risk of iridocyclitis(IVW:OR,1.17;95%CI,1.10-1.24,P=2.54×10^(-7)).CD was significantly associated with conjunctivitis(IVW:OR,1.05;95%CI,1.03-1.08,P=3.20×10^(-5)),keratitis(IVW:OR,1.06;95%CI,1.02-1.09;P=1.13×10^(-3)),and iridocyclitis(IVW:OR,1.09;95%CI,1.04-1.14;P=1.43×10^(-4)).CONCLUSION:IBD causally poses a risk of inflammation of conjunctiva,cornea,Iris-ciliary body complex,and optic neuritis.CD is more closely associated with the eye inflammation than UC.These impliy that the relationship of IBD and different parts of the eye structure are different,and provide novel evidence linking based on the association of the gut-eye axis.

Efficacy of Isotonic Seawater Solution on Inflammation of the Ocular Surface in Matrix Metalloproteinase MMP-9-Positive Dry Eye Disease Patients

Purpose: Prospective study to evaluate the anti-inflammatory efficacy of isotonic seawater solution on metalloproteinase 9 (MMP-9) levels in the tears of patients with dry eye disease (DED). Methods: A total of 50 patients were included, with the following dry eye criteria in both eyes: InflammaDry? test initially positive, ocular surface disease index (OSDI) score ≥ 12 and <33, tear film breakup time (TBUT) ≤ 10 seconds, Shirmer I test result ≤ 10 mm/5 minutes, corneal staining ≥ 1. Additionally, all the patients selected corresponded to a dry eye type 2 - 3 severity degree - mild and moderate - Dry Eye Workshop Study (DEWS) classification. The InflammaDry test is used to measure levels of MMP9 at the beginning and the end of the study. All patients were treated exclusively with isotonic seawater solution 5 times a day for 3 weeks. Results: The InflammaDry test was positive in 100% of the patients (n = 50) and in 100% (n = 100) of the eyes before treatment. In 14 (28%) patients the test became negative in both eyes, and in 15 (30%) it was negative in one of the eyes. In 43% (n = 43) of the positive eyes, MMP-9 became undetectable in the tear fluid following treatment with isotonic seawater. This change was statistically significant (p < 0.001). Conclusions: The washes with ophthalmic isotonic seawater solution have a significant impact on inflammation of the ocular surface in dry eye disease, with an ability to make MMP-9 levels negative in 43% of cases.

Behcet's disease-related panuveitis following COVID-19 vaccination:A case report

BACKGROUND Behcet's disease(BD)is an inflammatory disorder known for various symptoms,including oral and genital ulcers and ocular inflammation.Panuveitis,a severe eye condition,is rare as the first sign of BD.CASE SUMMARY We present an unusual case of a 30-year-old man who developed panuveitis after receiving the mRNA-based coronavirus disease 2019(COVID-19)vaccine(Moderna).Laboratory tests ruled out infections,but he had a positive HLA-B51 result and a history of genital ulcer and oral ulcers,leading to a BD diagnosis.Treatment with corticosteroids improved his condition.Interestingly,he had another episode of panuveitis after the second mRNA vaccine dose,which also responded to corticosteroids.CONCLUSION This case highlights the rare onset of BD following mRNA COVID-19 vaccination,suggesting a potential link between these vaccines and BD's eye symptoms,emphasizing the importance of quick treatment in similar cases.

AN EXPERIMENTAL STUDY OF THE INTERLEUKIN 1 LEVELS IN AQUEOUS HUMOR AFTER TRANSSCLERAL FIXATION OF INTRAOCULAR LENSES

Purpose. To study the interleukin 1 (IL-1)levels in aqueous humor after transscleral fixation of in- traocular lenses (IOLs) implantation in rabbits and discuss the effect of IL-1 on postoperative anterior ocular inflammation. Methods. Twenty-seven pigmented rabbits were divided into three groups: GI, transscleral fixation of posterior chamber (PC) IOLs implantation; G2, Lens of rabbits were removed without IOLs implanta- tion; G3, the control group, without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days, aqueous humor samples were obtained. Methyl thiazolyl tetrazolium (MTT) colormetry was used to detected for the presence of IL-1. The data were analyzed by using analysis of variance of SAS soft ware. Results’ It was found that IL-1 level in aqueous humor was increased after transscleral fixation of I- OLs implantation, IL-1 level reached its maximum on the 14th postoperative days in the IOL implanted group. IL-1 levels on 1st, 3rd, 7th and 14th days postoperatively was significantly higher (P<0. 05) in I- OLs implanted group than that of only extracapsular lenses extraction but no IOLs implantation group and that of the none surgical intervention group. COnclusions.IL-1 levels increased had a close relationship with a specific response to IOL implanta- tion. The increase of IL-1 may be suggested as the principal mediators of immunological and inflammatory responses, so that may play critical role in anterior ocular inflammative response after IOL implantation.

Inhibitory Effects of Flufenamic Acid and Mefenamic Acid on Experimental Uveitis in Rabbits

The experimental uveitis was induced by injecting lens protein into the antertor cham- ber of rabbit's eye.A special fluorophotometer was used for objectively measuring the flaoreseein level in the anterior chamber of the eve to rellect the degree of inflammation.When administered in- travenously.the inhibitory effects of flufenamic acid and mefenamic acid on experimental uveius showed a dose-dependent relationship,The former at dosages 5.0.12.5 and 250 mg kg decreased the areas under the time-response curve to 22.3%.11.5% and 9.3% of the control.respcctively:however the latter at dosages 6.2.12.5 and 25.0 mg/kg decreased the areas under the curve to 35.5%.21.0% and 8.6% of the control,respectively.When instilled by ocular route.50μl of 1% eye-drops of flufenmic acid or mefenamic acid lowered the fluoreseein levels of treated eyes as well as contra-lateral eyes.The areas under the time-response curve for treated eyes were decreased to 20.3% of the control and those of contra-lateral eyes to about 50% of the control.The results indicate that both flufenamic and mefenamic acids,applied intravenously or topically,can inhibit ocular inflammation.

Leptin's concentration in tears and dry eye:a clinical observational study

AIM:To investigate the concentration of leptin in tears and its correlation with dry eye symptoms and signs.METHODS:The study enrolled individuals(n=39)responding to an advertising or dry eye patients(n=58)from the Ophthalmology Department.Tear samples were collected for leptin concentration measuring.Ocular Surface Disease Index(OSDI),tear meniscus height(TMH),tear break up time(TBUT),cornea fluorescein staining,Schirmer test(ST)and impression cytology(IC)were assessed.Leptin concentration in tears of dry eye patients and healthy controls,and its correlation with clinical features of dry eye disease(DED)were analyzed.RESULTS:Age,body mass index(BMI),OSDI scores and cornea fluorescein staining scores showed a negative correlation with leptin concentration in tears(r=-0.340,P=0.001;r=-0.332,P=0.001;r=-0.258,P=0.011;r=-0.424,P<0.001,respectively).ST showed positive correlation with leptin concentration in tears(r=0.206,P=0.045).No significant difference was observed in leptin concentration between dry eye patients and controls(P=0.682).Multivariate linear regression analysis revealed that dry eye,OSDI,corneal fluorescein staining scores and ST correlated with leptin concentration in tears.CONCLUSION:This is the first study measuring leptin concentration in tears.The correlation between leptin concentration and DED symptoms and signs reveal that leptin level correlated with the dry eye,potentially contributing to repair of ocular damage and dry eye improvement.