A Genetic Case-Control Study Confirms the Implication of<i>SMAD7</i>and<i>TNF Locus</i>in the Development of Proliferative Vitreoretinopathy

Rojas, Jimena; Fernández, Itziar; Pastor, J. Carlos; MacLaren, Robert E.; Ramkissoon, Yashin; Harsum, Steven; Charteris, David G.; Meurs, Jan van; Amarakoon, Sankha; Ruiz-Moreno, José M.; Rocha‐Sousa, Amândio; Brión, Marı́a; Carracedo, Ángel

doi:10.1167/iovs.12-10931

Cited by 42 publications

(40 citation statements)

References 44 publications

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“…The TGF-b pathway is another potential target pointed out by our study (Rojas et al, 2013). SMAD7 is a mediator that acts as an inhibitor of the profibrotic action of TGF-b by blocking phosphorylation of SMAD2 and SMAD3.…”

Section: Designing New Strategies For Pvr Treatment Guided By Geneticsmentioning

confidence: 70%

“…Later, a replicated candidate gene association study confirmed the implication of the SMAD7 gene and the TNF locus in the pathogenesis of PVR (Rojas et al, 2010(Rojas et al, , 2013. In addition p53 and MDM2, genes that play roles in apoptosis, have been implicated in the development of PVR (Pastor-Idoate et al, 2013a.…”

Section: Genetics Of Pvrmentioning

confidence: 98%

“…We have begun to explore the genetic profile of PVR patients (Pastor-Idoate et al, 2013aRojas et al, 2009;Rojas et al, 2013;Sanabria Ruiz-Colmenares et al, 2006). We are convinced that genetics play an important role because the production of cytokines is a gene-regulated process (Zacks et al, 2006) and variations in these genes could be an important factor for PVR development.…”

Section: Our Ideas For the Pathogenesis Of Pvrmentioning

confidence: 99%

“…For example, in the identification of causative genes, functional SNPs or SNPs in linkage disequilibrium with causative genes could point out genes that have never been implicated in the disease, or they could confirm the role of other genes previously identified (Rojas et al, 2013).…”

Section: Usefulness Of Genetic Studies: Unraveling the Pathogenesis Omentioning

confidence: 99%

See 3 more Smart Citations

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

Pastor

Rojas

Pastor‐Idoate

et al. 2016

Progress in Retinal and Eye Research

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273

261

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Section: Designing New Strategies For Pvr Treatment Guided By Geneticsmentioning

confidence: 70%

Section: Genetics Of Pvrmentioning

confidence: 98%

Section: Our Ideas For the Pathogenesis Of Pvrmentioning

confidence: 99%

Section: Usefulness Of Genetic Studies: Unraveling the Pathogenesis Omentioning

confidence: 99%

See 2 more Smart Citations

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

Pastor

Rojas

Pastor‐Idoate

et al. 2016

Progress in Retinal and Eye Research

Self Cite

273

261

View full text Add to dashboard Cite

“…Ongoing research is focused on identifying candidate genes associated with a higher risk of PVR after RRD, and one of the main candidate genes is the lymphotoxin alpha (LTA) gene, which is located in the TNF locus [10].…”

Section: Clinical and Experimental Ophthalmologymentioning

confidence: 99%

Role of Systemic Anti-Tumor Necrosis Factor Alpha Treatment in the Reduction of Proliferative Vitreoretinopathy

Rosa¹,

Fernandez²,

Lipski³

2015

J Clin Exp Ophthalmol

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Objective: Proliferative vitreoretinopathy (PVR) is still one of the most serious complications of rhegmatogenous retinal detachment (RRD) because there is no effective treatment or prophylaxis. Tumor necrosis factor α (TNFα) has been implicated in the development of PVR. Thus, the blockade of this factor could reduce or prevent the onset of PVR. However, systemic treatment with anti-TNFα has some risks and side effects, and the use of these drugs in this situation is not yet justified. Therefore we sought an indirect approach to determine if systemic anti-TNFα provided any protection against the development of PVR after RRD surgery. We attempted to estimate the rate of RRD and PVR in patients who were treated systemically with anti-TNFα drugs because of autoimmune diseases and who also had surgically-treated RRD.Methods: Nine centers participated in this retrospective, observational study of cases and controls. Two different approaches were used to find cases and controls. The records at five clinical centers of patients who were under anti-TNFα treatment for chronic inflammatory systemic diseases between January 2004 and 2014 were reviewed to determine how many developed RRD. Additionally, the records in eight clinical centers of patients who underwent RRD surgery during this same period were reviewed to determine the numbers who were simultaneously receiving anti-TNFα treatment. Cases included patients treated with anti-TNFα treatment whereas controls were those who were not under anti-TNFα treatment. Both patients and controls had systemic inflammatory disease. The main outcome measure was development of PVR after RRD surgery at three months follow-up.Results: A total of 8,017 medical records from nine different centers were reviewed. Among the 1,884 patients with anti-TNFα treatment and 6,133 patients operated for primary RRD, only 3 controls and 1 case were identified.Conclusions: An insufficient number of patients were identified to allow any valid conclusion regarding our hypothesis that systemic anti-TNFα therapy could reduce the onset of PVR after RRD surgery. Nevertheless, this indirect approach could be useful for future research in PVR prevention.

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Analysis of Lymphotoxin Alpha Expression in Human Retina and Generation of Expression Vectors to Functional Characterization of Polymorphisms in the Tumor Necrosis Factor Locus

Fernandez-Bueno

Rodríguez-Hernández

González‐Sarmiento

et al. 2020

Methods in Molecular Biology

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A Genetic Case-Control Study Confirms the Implication ofSMAD7andTNF Locusin the Development of Proliferative Vitreoretinopathy

Abstract: These results confirm the genetic contribution to PVR and the implication of SMAD7 and TNF locus in the development of PVR. This finding may have implications for understanding the mechanisms of PVR and could provide a potential new therapeutic target for PVR prophylaxis.

Cited by 42 publications

References 44 publications

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences

Role of Systemic Anti-Tumor Necrosis Factor Alpha Treatment in the Reduction of Proliferative Vitreoretinopathy

Analysis of Lymphotoxin Alpha Expression in Human Retina and Generation of Expression Vectors to Functional Characterization of Polymorphisms in the Tumor Necrosis Factor Locus

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