SNP 309 del gen MDM2, como marcador de riesgo de la Vitreorretinopatia Proliferante Proyecto Retina 4

Propósito: comparar la distribución del polimorfismo 309 del gen MDM2 entre pacientes europeos sometidos a cirugía del desprendimiento de retina (DR) en relación con el posterior desarrollo de una vitreoretinopatía proliferante (VRP). Diseño: Como parte del proyecto Retina 4 (estudio Europeo multicéntrico, para el análisis del componente genético de la VRP), se llevo a cabo un estudio de asociación genética entre casos y controles. Participantes y controles: Se han genotipado 555 muestras de DNA procedentes de 134 pacientes con VRP secundaria a DR y 421 pacientes con DR sin VRP. Metodología: se analizó el polimorfismo (rs2279744) del gen MDM2, utilizando un primer específico mediante la técnica de PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism) en dos fases. Se estudio la proporción de los distintos genotipos, las frecuencias alélicas y los portadores homocigotos de Guanina (G) entre las diferentes muestras de los distintos países participantes (España, Portugal, Holanda y Gran Bretaña).También se comparó el genotipo y los portadores homocigotos (G/G) entre los casos y controles en la muestra global. Además se analizó la interacción genética entre los polimorfismos rs2279744 del gen MDM2 y el rs1042522 del gen p53, previamente estudiado por nuestro grupo. Principales variables: Asociaciones significativas simples con VRP. Resultados: Al analizar las frecuencias genotípicas de la posición 309 del intron 1 del gen MDM2, se encontraron diferencias significativas (p<0.05, Fisher test) entre los casos y controles de España y Portugal (Fase I), y también entre los casos y controles de Holanda y Gran Bretaña (Fase II). El análisis de los portadores homocigotos G/G entre casos y controles reveló diferencias entre España [35.1- 53.0]/[22.6-32.9], Portugal [39.0-74.4]/[21.4-38.9], Holanda [40.6-66.3]/[25.3- 38.8] y Gran Bretaña [37.5-62.4]/[23.3-34.2]. La odds ratio de los portadores G/G en las muestras conjuntas de España y Portugal fue de 5.4 (95% CI: 2.2-12.7, p<0.05), mientras que la odds ratio de los portadores de G/G en las muestras conjuntas de Holanda y Gran Bretaña fue de 7.3 (95% CI: 2.8-19.1 p<0.05). Todos los controles se encontraban bajo el equilibrio Hardy-Weinberg. Proyecto retina 4.Universidad de Valladolid. Instituto Universitario de Oftalmobiología Aplicada (IOBA)Máster en Subespecialidades Oftalmológica

iOCT in PVR Surgical Management

Recent advances in optical coherence tomography (OCT) technology have allowed the introduction of OCT into the operating room. Intraoperative OCT (iOCT) has been utilized to visualize the retinal architecture prior, during, and following several retinal surgical technics. The identification of epiretinal, subretinal, and intraretinal changes is one of the crucial points in PVR management. The iOCT can identify intraretinal changes and/or subretinal PVR membranes which cannot be easily peeled as epiretinal membranes. Intraretinal forms are especially difficult to identify preoperatively but their presence may be crucial in surgical management because the attempt to remove the presumed membrane may result in severe retinal tissue damage and iatrogenic tears. Therefore, surgical technique and even tamponade choice may be seriously affected by OCT imaging results

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.This work was supported by SAF 2007-66394, FIS PI10/00219 and Group of Excellence Grant (GR15) from Junta de Castilla y León.Peer Reviewe

Matrix metalloproteinases in age-related macular degeneration (AMD)

Producción CientíficaAge-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is the leading cause of vision loss and legal blindness among the elderly. Although the pathogenesis of AMD is still barely understood, recent studies have reported that disorders in the regulation of the extracellular matrix (ECM) play an important role in its etiopathogenesis. The dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). The present review focuses on the crucial processes that occur at the level of the Bruch’s membrane, with special emphasis on MMPs, TIMPs, and the polymorphisms associated with increased susceptibility to AMD development. A systematic literature search was performed, covering the years 1990–2020, using the following keywords: AMD, extracellular matrix, Bruch’s membrane, MMPs, TIMPs, and MMPs polymorphisms in AMD. In both early and advanced AMD, the pathological dynamic changes of ECM structural components are caused by the dysfunction of specific regulators and by the influence of other regulatory systems connected with both genetic and environmental factors. Better insight into the pathological role of MMP/TIMP complexes may lead to the development of new strategies for AMD treatment and prevention

Complications associated with the use of silicone oil in vitreoretinal surgery: A systemic review and meta‐analysis

Producción CientíficaSilicone oil (SO) still represents the main choice for long-term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta-analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case–control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re-detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty-three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27–2.18) and the rate of retinal re-detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50–0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)-emulsification rate was non-significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so-called unexplained vision loss, which affects a significant percentage of eyes. Re-detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low- and high-viscosity silicones. All these data warrant more standardized prospective studies

Hair cortisol level as a molecular biomarker in retinitis pigmentosa patients

Producción CientíficaPurpose: Retinitis pigmentosa (RP) patients commonly experience negative psychological states due to their progressive and unpredictable loss of vision and visual variations related to stress. The aim of this study was to examine hair cortisol concentrations (HCCs), which is usually associated with chronic stress, pretending to unveil possible associations between underlying psychological factors and disease severity in RP patients. Methods: Seventy-eight RP patients and 148 healthy controls were included in this study. A complete ophthalmological exam was performed in all patients to grade into severity disease groups. Perceived stress and trait-anxiety were measured by the State-Trait Anxiety Inventory (STAI) questionnaire. Results: Fifty-two (67%) patients had severe RP and 26 (33%) mild-moderate RP. Fifty-eight (58,9%) patients reported severely levels of stress and 18 (23.,1%) highly levels assessed by STAI questionnaire. RP patients exhibited higher HCCs (500.04 ± 120.99 pg/mg) than in controls (136.17 ± 60.51 pg/mg; p < 0.001). Severe RP patients had significant higher HCCs than mild-moderate patients differing in 274.27 pg/mg (p < 0.001). RP severity grade and perceived anxiety levels in the questionaries were not associated. Group differences were not affected by relevant covariates (age, grade of severity, stress status, and gender). Conclusions: HCC seems an effective biomarker associated with chronic stress in RP patients. This study shows that HCC in patients with RP are elevated compared to population-based controls, and association between HCC and RP severity was found. Future research is needed to characterize the effect of untreated negative psychological states on progression of the disease if any.Gerencia Regional de Salud de Castilla y León (GRS, 1932/A/19)Ministerio de Ciencia, Innovación y Universidades (grant PID2020-114585RA-I00

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR. Copyright

Hair cortisol level as a molecular biomarker in retinitis pigmentosa patients

Abstract Purpose: Retinitis pigmentosa (RP) patients commonly experience negative psychological states due to their progressive and unpredictable loss of vision and visual variations related to stress. The aim of this study was to examine hair cortisol concentrations (HCCs), which is usually associated with chronic stress, pretending to unveil possible associations between underlying psychological factors and disease severity in RP patients. Methods: Seventy-eight RP patients and 148 healthy controls were included in this study. A complete ophthalmological exam was performed in all patients to grade into severity disease groups. Perceived stress and trait-anxiety were measured by the State-Trait Anxiety Inventory (STAI) questionnaire. Results: Fifty-two (67%) patients had severe RP and 26 (33%) mild-moderate RP. Fifty-eight (58,9%) patients reported severely levels of stress and 18 (23.,1%) highly levels assessed by STAI questionnaire. RP patients exhibited higher HCCs (500.04 ± 120.99 pg/mg) than in controls (136.17 ± 60.51 pg/mg; p < 0.001). Severe RP patients had significant higher HCCs than mild-moderate patients differing in 274.27 pg/mg (p < 0.001). RP severity grade and perceived anxiety levels in the questionaries were not associated. Group differences were not affected by relevant covariates (age, grade of severity, stress status, and gender). Conclusions: HCC seems an effective biomarker associated with chronic stress in RP patients. This study shows that HCC in patients with RP are elevated compared to population-based controls, and association between HCC and RP severity was found. Future research is needed to characterize the effect of untreated negative psychological states on progression of the disease if any

The p53 Codon 72 Polymorphism (rs1042522) Is Associated with Proliferative Vitreoretinopathy

Abstract Purpose: To compare the distribution of a p53 gene polymorphism among European subjects undergoing primary retinal detachment (RD) surgery in relation to the development of proliferative vitreoretinopathy (PVR). Design: Case-controlled gene association study conducted as a component of the Retina 4 Project (a European multicenter study). Participants and controls: Five hundred fifty DNA samples, 134 with PVR secondary to primary RD and 416 with RD without PVR. Methods: The p53 codon 72 polymorphism (rs1042522) was analyzed using allele-specific primer polymerase chain reaction. Proportions of genotypes and the proline (Pro-P) homozygote groups between subsamples from different countries were analyzed in 2 phases. In the first, subsamples from Spain and Portugal were analyzed. After significant results were found, samples from the United Kingdom (UK) and The Netherlands were analyzed (second phase). Genotypic and allelic frequencies were compared between cases and controls in the global sample. Main outcome measures: Single significant associations with PVR. Results: A significant difference (P<0.05, Fisher exact test) was observed regarding the p53 genotype frequencies at codon 72 between the PVR cases and the non-PVR controls in Spain and Portugal (phase I), but not in the UK or The Netherlands (phase II). Analysis of Pro homozygote carriers between cases and controls revealed differences in Spain (29.01-42.18 and 2.29-10.20, respectively), Portugal (10.49-29.50 and 1.35-8.89, respectively), and The Netherlands (16.49-31.70 and 4.51-15.09, respectively), but no differences in the UK (7.68-18.1 and 4.85-13.94, respectively). The odds ratio of Pro carriers from Spain and Portugal together was 8.12 (95% confidence interval [CI], 3.72-17.69; P<0.05), whereas the odds ratio of Pro carriers from the UK and The Netherlands was 2.12 (95% CI, 0.96-4.68; P = 0.07). All control samples were in Hardy-Weinberg equilibrium. Considering the entire sample, significant differences were found in genotype frequencies between cases (RR, 30.59%; RP, 43.28%; PP, 26.11% [R = Arg; P = Pro]) and controls (RR, 39.66%; RP, 52.64%; PP, 7.69%) and in Pro homozygote carriers between controls (Pro homozygote 95% CI, 18.67-33.52) and cases (Pro homozygote 95% CI, 5.1-10.2). Conclusions: Results indicate that the Pro variant of p53 codon 72 polymorphism is associated with a higher risk of PVR developing after a primary RD. Further studies are necessary to understand the role of this polymorphism in the development of PVR