The genetics of retinopathy of prematurity: a model for neovascular retinal disease

Imaging and Informatics in ROP Research Consortium

Research output: Contribution to journalArticle

Abstract

TOPIC: Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease in premature infants, and is a major cause of childhood blindness worldwide. In addition to known clinical risk factors such as low birth weight and gestational age, there is a growing body of evidence supporting a genetic basis for ROP. CLINICAL RELEVANCE: While comorbidities and environmental factors have been identified as contributing to ROP outcomes in premature infants, most notably gestational age and oxygen, some infants progress to severe disease despite absence of these clinical risk factors. The contribution of genetic factors may explain these differences and allow better detection and treatment of infants at risk for severe ROP. METHODS: To comprehensively review genetic factors that potentially contribute to the development and severity of ROP, we conducted a literature search focusing on the genetic basis for ROP. Terms related to other heritable retinal vascular diseases like "familial exudative vitreoretinopathy", as well as to genes implicated in animal models of ROP, were also used to capture research in diseases with similar pathogenesis to ROP in humans with known genetic components. RESULTS: Contributions across several genetic domains are described including vascular endothelial growth factor, the Wnt signaling pathway, insulin-like growth factor 1, inflammatory mediators, and brain-derived neurotrophic factor. CONCLUSIONS: Most candidate gene studies of ROP have limitations such as inability to replicate results, conflicting results from various studies, small sample size, and differences in clinical characterization. Additional difficulty arises in separating the contribution of genetic factors like Wnt signaling to ROP and prematurity. Although studies have implicated involvement of multiple signaling pathways in ROP, the genetics of ROP have not been clearly elucidated. Next-generation sequencing and genome-wide association studies have potential to expand future understanding of underlying genetic risk factors and pathophysiology of ROP.

Original languageEnglish (US)
Pages (from-to)949-962
Number of pages14
JournalOphthalmology. Retina
Volume2
Issue number9
DOIs
StatePublished - Sep 1 2018

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Retinal Diseases
Retinopathy of Prematurity
Retinal Vessels
Vascular Diseases
Premature Infants
Gestational Age
Wnt Proteins
Wnt Signaling Pathway
Genome-Wide Association Study
Brain-Derived Neurotrophic Factor
Low Birth Weight Infant
Somatomedins
Blindness
Sample Size
Vascular Endothelial Growth Factor A
Genes
Comorbidity

ASJC Scopus subject areas

  • Nephrology

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The genetics of retinopathy of prematurity : a model for neovascular retinal disease. / Imaging and Informatics in ROP Research Consortium.

In: Ophthalmology. Retina, Vol. 2, No. 9, 01.09.2018, p. 949-962.

Research output: Contribution to journalArticle

Imaging and Informatics in ROP Research Consortium. / The genetics of retinopathy of prematurity : a model for neovascular retinal disease. In: Ophthalmology. Retina. 2018 ; Vol. 2, No. 9. pp. 949-962.
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abstract = "TOPIC: Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease in premature infants, and is a major cause of childhood blindness worldwide. In addition to known clinical risk factors such as low birth weight and gestational age, there is a growing body of evidence supporting a genetic basis for ROP. CLINICAL RELEVANCE: While comorbidities and environmental factors have been identified as contributing to ROP outcomes in premature infants, most notably gestational age and oxygen, some infants progress to severe disease despite absence of these clinical risk factors. The contribution of genetic factors may explain these differences and allow better detection and treatment of infants at risk for severe ROP. METHODS: To comprehensively review genetic factors that potentially contribute to the development and severity of ROP, we conducted a literature search focusing on the genetic basis for ROP. Terms related to other heritable retinal vascular diseases like {"}familial exudative vitreoretinopathy{"}, as well as to genes implicated in animal models of ROP, were also used to capture research in diseases with similar pathogenesis to ROP in humans with known genetic components. RESULTS: Contributions across several genetic domains are described including vascular endothelial growth factor, the Wnt signaling pathway, insulin-like growth factor 1, inflammatory mediators, and brain-derived neurotrophic factor. CONCLUSIONS: Most candidate gene studies of ROP have limitations such as inability to replicate results, conflicting results from various studies, small sample size, and differences in clinical characterization. Additional difficulty arises in separating the contribution of genetic factors like Wnt signaling to ROP and prematurity. Although studies have implicated involvement of multiple signaling pathways in ROP, the genetics of ROP have not been clearly elucidated. Next-generation sequencing and genome-wide association studies have potential to expand future understanding of underlying genetic risk factors and pathophysiology of ROP.",
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