The pathophysiology of retinopathy of prematurity: An update of previous and recent knowledge

Giacomo Cavallaro, Luca Filippi, Paola Bagnoli, Giancarlo La Marca, Gloria Cristofori, Genny Raffaeli, Letizia Padrini, Gabriella Araimo, Monica Fumagalli, Michela Groppo, Massimo Dal Monte, Silvia Osnaghi, Patrizio Fiorini, Fabio Mosca

Research output: Contribution to journalArticle

Abstract

Retinopathy of prematurity (ROP) is a disease that can cause blindness in very low birthweight infants. The incidence of ROP is closely correlated with the weight and the gestational age at birth. Despite current therapies, ROP continues to be a highly debilitating disease. Our advancing knowledge of the pathogenesis of ROP has encouraged investigations into new antivasculogenic therapies. The purpose of this article is to review the findings on the pathophysiological mechanisms that contribute to the transition between the first and second phases of ROP and to investigate new potential therapies. Oxygen has been well characterized for the key role that it plays in retinal neoangiogenesis. Low or high levels of pO2 regulate the normal or abnormal production of hypoxia-inducible factor 1 and vascular endothelial growth factors (VEGF), which are the predominant regulators of retinal angiogenesis. Although low oxygen saturation appears to reduce the risk of severe ROP when carefully controlled within the first few weeks of life, the optimal level of saturation still remains uncertain. IGF-1 and Epo are fundamentally required during both phases of ROP, as alterations in their protein levels can modulate disease progression. Therefore, rhIGF-1 and rhEpo were tested for their abilities to prevent the loss of vasculature during the first phase of ROP, whereas anti-VEGF drugs were tested during the second phase. At present, previous hypotheses concerning ROP should be amended with new pathogenetic theories. Studies on the role of genetic components, nitric oxide, adenosine, apelin and β-adrenergic receptor have revealed new possibilities for the treatment of ROP. The genetic hypothesis that single-nucleotide polymorphisms within the β-ARs play an active role in the pathogenesis of ROP suggests the concept of disease prevention using β-blockers. In conclusion, all factors that can mediate the progression from the avascular to the proliferative phase might have significant implications for the further understanding and treatment of ROP.

Original languageEnglish
Pages (from-to)2-20
Number of pages19
JournalActa Ophthalmologica
Volume92
Issue number1
DOIs
Publication statusPublished - Feb 2014

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Retinopathy of Prematurity
Vascular Endothelial Growth Factors
Oxygen
Hypoxia-Inducible Factor 1
Blindness
Insulin-Like Growth Factor I
Adenosine
Adrenergic Receptors
Gestational Age
Single Nucleotide Polymorphism
Disease Progression
Nitric Oxide
Therapeutics

Keywords

  • β-adrenergic receptors
  • erythropoietin
  • hypoxia-inducible factor 1
  • insulin-like growth factor-1
  • neovascularization
  • pathophysiology
  • placental growth factor
  • retinopathy of prematurity
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Ophthalmology

Cite this

The pathophysiology of retinopathy of prematurity : An update of previous and recent knowledge. / Cavallaro, Giacomo; Filippi, Luca; Bagnoli, Paola; La Marca, Giancarlo; Cristofori, Gloria; Raffaeli, Genny; Padrini, Letizia; Araimo, Gabriella; Fumagalli, Monica; Groppo, Michela; Dal Monte, Massimo; Osnaghi, Silvia; Fiorini, Patrizio; Mosca, Fabio.

In: Acta Ophthalmologica, Vol. 92, No. 1, 02.2014, p. 2-20.

Research output: Contribution to journalArticle

Cavallaro, G, Filippi, L, Bagnoli, P, La Marca, G, Cristofori, G, Raffaeli, G, Padrini, L, Araimo, G, Fumagalli, M, Groppo, M, Dal Monte, M, Osnaghi, S, Fiorini, P & Mosca, F 2014, 'The pathophysiology of retinopathy of prematurity: An update of previous and recent knowledge', Acta Ophthalmologica, vol. 92, no. 1, pp. 2-20. https://doi.org/10.1111/aos.12049
Cavallaro, Giacomo ; Filippi, Luca ; Bagnoli, Paola ; La Marca, Giancarlo ; Cristofori, Gloria ; Raffaeli, Genny ; Padrini, Letizia ; Araimo, Gabriella ; Fumagalli, Monica ; Groppo, Michela ; Dal Monte, Massimo ; Osnaghi, Silvia ; Fiorini, Patrizio ; Mosca, Fabio. / The pathophysiology of retinopathy of prematurity : An update of previous and recent knowledge. In: Acta Ophthalmologica. 2014 ; Vol. 92, No. 1. pp. 2-20.
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