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Inderjeet Kaur, Sonika Rathi, Subhadra Jalali, Divya Balakrishnan, Preeti P Chhablani, Ramesh Kekunaya, Subhabrata Chakrabarti; Global Gene Expression Profiling Among Different Stages of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3444.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP) is a vaso-proliferative eye disease of prematurely born infants with low birth weight . More than 50% of premature infants weighing less than 1250g at birth show evidence of ROP, and about 10% of these develop severe ROP. ROP regresses spontaneously in some infants while for others it progresses to severe stages in spite of similar antenatal and prenatal conditions. The major challenge of ROP management, therefore, is to distinguish the subgroup of infants who will not have spontaneous regression and would develop severe ROP. The present study was aimed at identifying the potential candidate genes and their pathways that may be responsible for the progression of ROP by comparing the global gene expression profiles across different stages of ROP.
RNA was isolated from blood samples of 15 preterm babies (GA ≤ 35 weeks and/or BW ≤ 1700 g) with different stages of ROP and 9 No-ROP preterm and 3 full term infants with no retinal disease . Global gene expression (~47,000 transcripts) analysis was performed using Illumina bead Chip array. Differential expression was analyzed using Genome Studio software and appropriate statistical tests. The important gene networks and pathways for ROP were identified for the differentially expressed genes with >2 fold change using Gene Ontology (GO) and Pathway analysis softwares.
Microarray analysis between patients of any stages of ROP compared to the premature controls showed differential expression of 142 genes of which, 115 genes were upregulated and 27 downregulated. 634 genes were found to be differentially expressed (337 upregulated and 297 downregulated) among proliferative ROP versus non proliferative ROP subjects of which 67 genes showed >2-fold change of expression. However for proliferative versus no ROP premature subjects, only 117 genes showed differential expression (30 upregulated and 94 downregulated). Further, pathway analysis of the differentially expressed genes (including CCL8, NOS3, AXIN2, TNF, CD40LG, BP1, HLA-DRB5, HLA-DRB1, NLRP2, CEC4D ) revealed inflammatory pathways like toll receptor and inflammation mediated by chemokine and angiogenic pathways like Wnt and endothelin signaling as the major pathways to be involved in ROP pathogenesis.
Genes involved in development, angiogenesis and immune response may be involved in the progression of mild ROP to more severe stages.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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