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Molecular Mechanisms in the Pathogenesis of Retinopathy of Prematurity (ROP)

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Abstract

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Neovascularization of retina in ROP eyes is a result of complex mechanisms that involve plethora of risk factors; however, the exact pathophysiology is still not clear. Even in the absence of risk factors, the disease progress to severe conditions. Thus, understanding the role of cellular molecules/events involved in ROP pathogenesis is very important to check the disease progression. Many studies have focused on investigating the role of cellular macromolecules and oxidative stress in ROP and their functional validations. The aim of this chapter is to discuss the role of various genes, RNA, proteins, lipids, and oxidative stress in physiological mechanism of normal retinal vascularization and various pathological changes that can lead to neovascularization of retina. The identification of such molecular mechanisms involved in neovascularization can help to find out novel therapeutic targets for an effective disease management.

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Abbreviations

AGTR1 :

Angiotensin II receptor type 1

Ang2 :

Angiopoietin-2

ANGPT2 :

Angiopoietin 2 gene

BDNF :

Brain-derived neurotrophic factor

BH4:

Tetrahydrobiopterin

BRB:

Blood–retinal barrier

BW:

Birth weight

C3 :

Complement C3

CETP :

Cholesteryl Ester Transfer Protein

CFB :

Complement Factor B

CFH :

Complement Factor H

CXCR4 :

C-X-C Motif Chemokine Receptor 4

CYP:

Cytochrome P450

DNA:

Deoxyribonucleic acid

EEQs:

Epoxyeicostetraenoic acid

EPA:

Eicosapentaenoic acid

EPAS1 :

Endothelial PAS domain-containing protein 1

EPO:

Erythropoietin

EPOR:

Erythropoietin receptor

FBLN5 :

Fibulin 5

FEVR:

Familial exudative vitreoretinopathy

FLT1:

fms-related tyrosine kinase-1

FZD:

Frizzled

FZD4 :

Frizzled 4

GA:

Gestational age

GP1BA :

Glycoprotein Ib-alpha

GPX:

Glutathione peroxidase

H2AFX :

H2A histone family member X

HIF-1:

Hypoxia-induced growth factor-1

IFN:

Interferons

IGF-1:

Insulin-like growth factors

IHH :

Indian Hedgehog Signaling Molecule

IL-1ra:

Interleukin-1 receptor antagonist

IL6:

Interleukin 6

IL8:

Interleukin 8

JAK:

Janus kinases

KDR:

Kinase insert domain receptor

Keap1:

Kelch-like ECH-associated protein 1

LRP5 :

Low-density lipoprotein receptor-related protein 5

MAPK:

Mitogen-activated protein kinase

MCP:

Monocyte chemoattractant protein

MCP-1:

Monocyte chemotactic protein 1

MIP-1a :

Macrophage Inflammatory Proteins

miRNA:

Micro RNA

MMP2 :

Matrix metallopeptidase 2

MMP9:

Matrix metallopeptidase 9

MMTV:

Mouse mammary tumor virus

mRNA:

Messenger RNAs

NADPH:

Nicotinamide adenine dinucleotide phosphate

NDP :

Norrie Disease Protein

NOS:

Nitric oxide synthase

Nrf2:

Nuclear factor erythroid 2-like 2

OIR:

Oxidative stress-induced retinopathy

p62:

p62/SQSTM1

PDGF :

Platelet-derived growth factor

PI3K:

Phosphoinisitol-3-kinase

PIGF:

Placental growth factor

PMN:

Polymorphonuclear neutrophils

Prx:

Peroxiredoxins

PUFAs:

Polyunsaturated fatty acids

RANTES:

Regulated upon Activation, Normal T Cell Expressed and Presumably secreted

RNA:

Ribonucleic Acid

ROI:

Reactive Oxygen Intermediates

ROP:

Retinopathy of prematurity

ROS:

Reactive oxygen species

SDF-1 :

Stromal cell-derived factor-1

SNP:

Single nucleotide polymorphism

STAT:

Signal transducer and activator of transcription proteins

TBX5 :

T-Box Transcription Factor 5

TGFβ1:

Transforming growth factor beta-1

TNFα:

Tumor necrosis factor alpha

TSPAN12 :

Tetraspanin-12

UTR:

Untranslated Region

VEGF:

Vascular endothelial growth factor

VEGFR1 :

Vascular endothelial growth factor receptor 1

VEGFR2:

Vascular endothelial growth factor receptor 2

VHL:

Von Hippel—Lindau protein

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  1. Prof. Brien Holden Eye Research Centre, KAR Campus, L V Prasad Eye Institute, Hyderabad, India

    Tarandeep Kaur, Satish Patnaik, Saurabh Kumar & Inderjeet Kaur

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  1. Department of Ophthalmology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Madhya Pradesh, India

    H. V. Nema

  2. Department of Ophthalmology, Sri Aurobindo Medical College and PG Institute, Indore, Madhya Pradesh, India

    Nitin Nema

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Kaur, T., Patnaik, S., Kumar, S., Kaur, I. (2022). Molecular Mechanisms in the Pathogenesis of Retinopathy of Prematurity (ROP). In: Nema, H.V., Nema, N. (eds) Genetics of Ocular Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-16-4247-0_9

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