MIF promoter polymorphisms are associated with epiretinal membrane but not retinal detachment with PVR in an american population.
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ABSTRACT:
SUBMITTER: Cebulla CM
PROVIDER: S-EPMC6698405 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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MIF promoter polymorphisms are associated with epiretinal membrane but not retinal detachment with PVR in an american population.
Cebulla Colleen M CM Stevenson William W Van Law Heather H Heisler-Taylor Tyler T Hamadmad Sumaya S Shah Mohd Hussain MH Kim Bongsu B Davidorf Frederick H FH Ohr Matthew M Wells Michael M Yanoga Fatoumata F Chang Susie S Terrell William W Miller Daniel M DM Klisovic Dino D Allen John B JB Shah Niraj N Geraymovych Elena E Tarabishy Ahmad B AB Kondapalli Srinivas S SS Brewington Beatrice Y BY Inman Andrea A Williams Demarcus D Kusibati Rania R Mathias Jay J Vedat Yildiz Y Fernandez Soledad S Wisely C Ellis CE Pilarski Robert R Abdel-Rahman Mohamed H MH
Experimental eye research 20190517
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Project description:PurposeVarious profibrotic and proinflammatory cytokines have been found upregulated in uncomplicated primary retinal detachment (pRD), but without providing a uniform picture. Here, we compare the cyto- and chemokine profiles in pRD with and without proliferative vitreoretinopathy (PVR) in an attempt to unravel relevant differences not in single cytokines, but in the cytokine profiles at diagnosis.MethodsUndiluted vitreous fluid (VF) was obtained at the beginning of surgery from 174 eyes with pRD without relevant PVR (maximally grade B; group 1; n = 81) and with moderate or advanced PVR requiring a gas tamponade (group 2; n = 49) or silicon oil filling (group 3; n = 44). VF of eyes undergoing macular hole (MH) surgery served as controls (group 4; n = 26). Forty-three cytokines were quantified in parallel using a multiplex cytokine analysis system (Bioplex). For all comparisons we applied Holm's correction to control for multiple comparisons.Results44.9% of group 2 eyes presented grade C1 and 55.1% C2-C3, whereas 86.4% of group 3 eyes exhibited a PVR grade of C2-D. CCL19 was the only cytokine that displayed higher concentrations in the vitreous of eyes with PVR C1 compared to lower PVR grades. Eyes with PVR C2-D showed higher levels of CCL27, CXCL6, IL4, IL16, CXCL10, CCL8, CCL22, MIG/CXCL9, CCL15, CCL19, CCL 23 and CXCL12 compared to controls. Interestingly, no difference of cytokine levels was detected between C1 and C2-D PVR.ConclusionsCCL19 may represent a potential biomarker for early PVR progression that holds promise for future diagnostic and therapeutic applications.
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Project description:The aim of this study was to compare changes in refraction following lens-sparing vitrectomy between patients with rhegmatogenous retinal detachment (RRD) and epiretinal membrane (ERM) and to investigate factors associated with the change in refraction.We reviewed medical records of 49 eyes of 49 patients with RRD (53.6 ± 7.8 years, mean ± standard deviation) and 24 eyes of 24 patients with ERM (50.9 ± 15.7 years) who underwent lens-sparing vitrectomy. Spherical equivalent refractive power was evaluated before and up to 18 months after surgery. The relationship between the change in refraction and several parameters was evaluated.A significant progressive myopic shift in refractive power was observed after vitrectomy in operated RRD and ERM eyes (P < 0.001, P = 0.016, respectively), with no significant difference in fellow eyes. The refraction values observed at ≥3 and ≥12 months following vitrectomy were significantly different as compared with those observed at baseline in the RRD group (P < 0.001) and the ERM group (P < 0.05), respectively. The change in refraction between the RRD and ERM groups was significant (P = 0.030). The multiple linear regression analysis showed that only age was significantly correlated with the change in refraction in RRD (P = 0.018) and ERM (P < 0.001) groups. The change in refraction was significantly and positively correlated with age in RRD (r = -0.461, P = 0.001) and ERM (r = -0.687, P < 0.001) groups. Following lens-sparing vitrectomy, cataract surgery was performed on 30 eyes after 0.89 ± 0.26 years in the RRD group and on 10 eyes after 1.11 ± 0.14 years in the ERM group; there was a significant difference in time to cataract surgery between the groups (P = 0.007). Kaplan-Meier survival analysis demonstrated that there was a significant difference in the rate of cataract surgeries between the RRD and ERM groups (P = 0.022).Following lens-sparing vitrectomy for RRD and ERM, a progressive myopic shift in refraction owing to nuclear sclerosis was observed. Core vitrectomy itself would cause a myopic shift of refraction. The only risk factor associated with cataract progression following lens-sparing vitrectomy is age for both types of patients.
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Project description:IntroductionAmniotic membrane (AM) is a popular treatment for external ocular diseases. First intraocular implantations in other diseases reported promising results. Here, we review three cases of intravitreal epiretinal human AM (iehAM) transplantation as an adjunct treatment for complicated retinal detachment and analyze clinical safety. Possible cellular rejection reactions against the explanted iehAM were evaluated and its influence was assessed on three retinal cell lines in vitro.MethodsThree patients with complicated retinal detachment and implanted iehAM during pars plana vitrectomy are retrospectively presented. After removal of the iehAM at subsequent surgery, tissue-specific cellular responses were studied by light microscopy and immunohistochemical staining. We investigated the influence of AM in vitro on retinal pigment epithelial cells (ARPE-19), Müller cells (Mio-M1), and differentiated retinal neuroblasts (661W) . An anti-histone DNA ELISA for cell apoptosis, a BrdU ELISA for cell proliferation, a WST-1 assay for cell viability, and a live/dead assay for cell death were performed.ResultsDespite the severity of the retinal detachment, stable clinical outcomes were obtained in all three cases. Immunostaining of the explanted iehAM showed no evidence of cellular immunological rejection. In vitro, there was no statistical significant change in cell death or cell viability nor were proliferative effects detected on ARPE-19, Müller cells, and retinal neuroblasts exposed to AM.ConclusioniehAM was a viable adjuvant with many potential benefits for treatment of complicated retinal detachment. Our investigations could not detect any signs of rejection reactions or toxicity. Further studies are needed to evaluate this potential in more detail.
| S-EPMC10164220 | biostudies-literature
Project description:This study investigated postoperative changes in metamorphopsia and aniseikonia in eyes that underwent vitrectomy for epiretinal membrane (ERM), macular hole (MH), or rhegmatogenous retinal detachment (RRD). In total, 166 eyes were included from 166 patients with ERM, MH, or RRD who underwent primary vitrectomy. Metamorphopsia and aniseikonia were quantified by M-CHARTS and the New Aniseikonia Test (NAT). Best-corrected visual acuity (BCVA), M-CHARTS, NAT assessments, and OCT examination were performed at 1, 3, and 6 months postoperatively. Of the 166 eyes, 65 had ERM, 21 had MH, 42 had macula-off RRD, and 38 had macula-on RRD. BCVA improved significantly between 1 and 6 months postoperatively in eyes with ERM, MH, and macula-off RRD (P = 0.0057, P = 0.0065, and P = 0.0021, respectively). M-CHARTS scores at 1 month postoperatively significantly decreased in eyes with ERM (P = 0.0034) and tended to decrease in eyes with MH (P = 0.068). NAT scores did not change between baseline and 1 month postoperatively in eyes with ERM or MH. Between 1 and 6 months postoperatively, M-CHARTS and NAT scores significantly decreased in eyes with macula-off RRD (P = 0.0064 and P = 0.0009, respectively), but not in eyes with ERM, MH, or macula-on RRD. At 6 months postoperatively, significant metamorphopsia was evident in 33.3% of eyes with ERM, 29.2% of eyes with MH, and 35.7% of eyes with macula-off RRD; 61.5% of eyes with ERM showed macropsia and 52.3% of eyes with macula-off RRD showed micropsia. In eyes with ERM, more central retinal thickness (CRT) correlated with postoperative BCVA, and deep retinal folds on enface OCT image correlated with postoperative metamorphopsia. In eyes with macula-off RRD, less CRT correlated with postoperative BCVA, and tended to correlate with postoperative micropsia. Macular morphologies could contribute to differences in postoperative visual acuity, metamorphopsia, and aniseikonia.
| S-EPMC7209121 | biostudies-literature
Project description:PurposeTo evaluate the time course of changes in the thickness of retinal layers after epiretinal membrane (ERM) removal surgery.MethodsA retrospective cohort study of patients following surgery for idiopathic ERM. We used new specialized image analysis software to create a thickness map of each retinal layer and analyzed changes during one year follow-up. Healthy fellow eyes were used as negative controls and the retina prior to surgery as positive control.ResultsTwenty-one patients were included with a mean age of 68±13 years. Central macular thickness decreased steadily until 6 months after surgery (25% decrease, 516±76 to 386±73 μm, P<0.001) with no further decrease between 6 and 12 months (386±73 to 390±73 μm, P=0.291). The retinal nerve fiber layer (RNFL), and the ganglion cell and inner plexiform layer (GCIPL) were most affected (57%, P<0.001 and 27%, P=0.010, respectively). The thickest region showed a more abrupt decrease of 21% at first follow-up (504±61 to 399±58 μm, P=0.001) with subsequent decrements of about 3%. Prior to surgery all retinal layers were thicker in study eyes compared with healthy control eyes (6-63%, all P<0.05).ConclusionsFollowing ERM surgery, in the course of 6 months, the macula gradually becomes thinner after which a stable state is reached. All layers appear to be affected, with the RNFL and GCIPL impacted the most. Our results provide a unique view on how the thickness of different retinal layers changes following ERM surgery.
| S-EPMC5848276 | biostudies-literature
Project description:Photoreceptor death and retinal gliosis underlie the majority of vision threatening retinal diseases including retinal detachment (RD). Although the underlying pathobiology of vision limiting processes in RD is not fully understood, inflammation is known to play a critical role. We conducted an iTRAQ proteomic screen of up- and down-regulated proteins in a murine model of RD to identify potential targetable candidates. Macrophage migration inhibitory factor (MIF) was identified and evaluated for neurotoxic and pro-gliotic effects during RD. Systemic administration of the MIF inhibitor ISO-1 significantly blocked photoreceptor apoptosis, outer nuclear layer (ONL) thinning, and retinal gliosis. ISO-1 and MIF knockout (MIFKO) had greater accumulation of Müller glia pERK expression in the detached retina, suggesting that Müller survival pathways might underlie the neuroprotective response. Our data show the feasibility of the MIF-inhibitor ISO-1 to block pathological damage responses in retinal detachment and provide a rationale to explore MIF inhibition as a potential therapeutic option for RD.
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Project description:BackgroundNumerous studies suggest that inflammation plays a key role in suicidal behavior. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has received increasing attention in depression research. However, no study has investigated whether MIF has genetic involvement in completed suicide. In this study, we sought to explore the relationship between two functional polymorphisms on the MIF gene promoter (MIF-794CATT5-8 microsatellite and MIF-173G/C single-nucleotide polymorphism [SNP]) and completed suicide by using one of the largest samples of suicide completers ever reported.MethodsThe subjects comprised 602 suicide completers and 728 healthy controls. We genotyped MIF-794CATT5-8 microsatellite by polymerase chain reaction-based size discrimination assay and MIF-173G/C SNP by TaqMan® SNP genotyping assay. The allele-, genotype-, or haplotype-based association analyses between the suicide completers and the controls were carried out with the χ2 test, the Cochran-Armitage trend test, or Fisher's exact test.ResultsAnalyses of allele or genotype frequency distributions of the polymorphisms studied here did not reveal any significant differences between the suicide completers and the controls. Haplotype analysis also revealed no association with completed suicide.ConclusionTo our knowledge, this is the first study that has examined the genetic association between MIF and completed suicide. Our results suggest that the effects of MIF-794CATT5-8 microsatellite and MIF-173G/C SNP on the MIF gene promoter might not contribute to the genetic risk of completed suicide in the Japanese population.
| S-EPMC5370383 | biostudies-literature
Project description:PurposeTo evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies.MethodsStudies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well.ResultsFive uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = -0.28, 95% CI = -0.37, -0.20; p < 0.001), but with significant heterogeneity. In either group, mean BCVA significantly improved following the implant (in the ERM group, MD = -0.31, 95% CI = -0.40, -0.22; in the RD group, MD = -0.22, 95% CI = -0.41, -0.03), with no difference between the two groups (p=0.41). However, there was significant heterogeneity in both groups. Considering the last available follow-up, a significant CMT reduction was found in the overall population, irrespective of the indication for vitrectomy (MD = -129.75, 95% CI = -157.49, -102.01; p < 0.001). In the ERM group, a significant CMT reduction was shown following DEX (MD = -133.41, 95% CI = -155.37, -111.45; p < 0.001), with no heterogeneity. In the RD group, mean CMT reduction was borderline significant (MD = -128.37, 95% CI = -253.57, -3.18; p=0.040), with significant heterogeneity. No difference in CMT improvement was found between the two groups (p=0.94).ConclusionThis meta-analysis showed that DEX yielded a significant improvement in visual and anatomical outcomes, even if limited by significant heterogeneity. Dexamethasone implant represents an effective treatment for postoperative macular oedema secondary to ERM and RD vitrectomy.
| S-EPMC8064798 | biostudies-literature
Project description:We investigated the effect of retinal traction caused by epiretinal membranes (ERMs) on aniseikonia and retinal microstructures in 81 unilateral ERMs. Retinal traction was quantified by measuring the maximum depth of the retinal fold (MDRF) using en face optical coherence tomography (OCT) images. Measurements included the mean inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), central retinal thickness (CRT), and interocular ratios of the foveal avascular zone (FAZ) area (FAZ ratio). Significant correlations were found between the preoperative MDRF and preoperative aniseikonia (P < 0.001), INL thickness (P < 0.001), CRT (P < 0.001), and FAZ ratio (P = 0.003). Preoperative aniseikonia was significantly correlated with preoperative INL and OPL-ONL thicknesses (P < 0.001 and P = 0.020, respectively) and CRT (P = 0.003). Multiple regression analysis revealed that preoperative aniseikonia was significantly associated with preoperative MDRF, INL, and OPL-ONL thicknesses (P = 0.029, 0.006, and 0.006, respectively). Twenty-nine eyes underwent membrane peeling, resolving all retinal folds 6 months postoperatively. A significant correlation was observed between preoperative MDRF and postoperative aniseikonia (P = 0.011). Our findings suggest that retinal traction by ERM is significantly associated with aniseikonia both pre- and postoperatively, alongside other OCT parameters.
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Project description:Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.
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