Chapter 6
The effects of hypoxia, hyperoxia, and oxygen fluctuations on oxidative signaling in the preterm infant and on retinopathy of prematurity
M. Elizabeth Hartnett,
M. Elizabeth Hartnett
Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, UT, USA
Search for more papers by this authorM. Elizabeth Hartnett,
M. Elizabeth Hartnett
Department of Ophthalmology, Moran Eye Center, University of Utah, Salt Lake City, UT, USA
Search for more papers by this authorBook Editor(s):Donald Armstrong,
Robert D. Stratton,
Donald Armstrong
Department of Biotechnical and Clinical Laboratory Sciences, State University of New York at Buffalo, Buffalo, NY, USA
Search for more papers by this authorRobert D. Stratton
Department of Ophthamology, University of Florida College of Medicine, Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, US
Search for more papers by this authorFirst published: 29 January 2016
Summary
This chapter defines retinopathy of prematurity (ROP) and reviews the relationship between oxygen levels and oxidative stress in preterm birth and term birth. The chapter also reviews the role of current-day oxygen stresses including high oxygen and fluctuations in oxygenation in activating oxidative signaling pathways that can lead to normal or aberrant retinal vascular development. The combination of fluctuations in oxygenation with periodic hyperoxia and hypoxia leads to the first phase of ROP known as delayed physiologic retinal vascular development (PRVD). In human preterm infants, retinal detachment can occur because of fibrovascular changes that occur between vasoproliferation and the vitreous. The supplemental therapeutic oxygen to prevent retinopathy of prematurity (STOP-ROP) tested the hypothesis that higher oxygen saturation targets would reduce vasoproliferation and reduce the number of eyes reaching the threshold level of the severity of ROP.
References
- Good, W.V., Hardy, R.J., Dobson, V. et al. (2005) The incidence and course of retinopathy of prematurity: findings from the early treatment for retinopathy of prematurity study. Pediatrics, 116, 15–23.
- Shah, P.K., Narendran, V. & Kalpana, N. (2012) Aggressive posterior retinopathy of prematurity in large preterm babies in South India. Archives of Disease in Childhood Fetal and Neonatal Edition, 97, F371–5.
- Mann, I. (1964) The Development of the Human Eye, 1st edn. Grune and Stratton Inc., New York.
- McLeod, D.S., Hasegawa, T., Prow, T., Merges, C. & Lutty, G. (2006) The initial fetal human retinal vasculature develops by vasculogenesis. Developmental Dynamics, 235, 3336–47.
- Hartnett, M.E. (2014) Retinopathy of prematurity: a template for studying retinal vascular disease. In: L.M. Chalupa & J.S. Werner (eds), The New Visual Neurosciences. MIT Press, Cambridge MA, pp. 1483–1502.
-
Hartnett, M.E. & DeAngelis, M.M. (2012) Studies on retinal and choroidal disorders. In: D. Armstrong (ed), Studies on Retinal and Choroidal Disorders, 1st edn. Humana Press, New York, pp. 559–584.
10.1007/978-1-61779-606-7_28 Google Scholar
- Bizzarro, M.J., Hussain, N., Jonsson, B. et al. (2006) Genetic susceptibility to retinopathy of prematurity. Pediatrics, 118, 1858–1863.
- Buhimschi, I.A., Buhimschi, C.S., Pupkin, M. & Weiner, C.P. (2003) Beneficial impact of term labor: Nonenzymatic antioxidant reserve in the human fetus. American Journal of Obstetrics and Gynecology, 189, 181–188.
- Sanchez-Alvarez, R., Almeida, A. & Medina, J.M. (2002) Oxidative stress in preterm rat Brain is due to mitochondrial dysfunction. [Article]. Pediatric Research, 51, 34–39.
- Najarian, T., Hardy, P., Hou, X. et al. (2000) Preservation of neural function in the perinate by high PGE2 levels acting via EP2 receptors. Journal of Applied Physiology, 89, 777–784.
- Wang, H., Zhang, S.X. & Hartnett, M.E. (2013) Signaling pathways triggered by oxidative stress that mediate features of severe retinopathy of prematurity. JAMA Ophthalmology, 131, 80–85.
-
Terry, T.L. (1942) Extreme prematurity and fibroblastic overgrowth of persistent vascular sheath behind each crystalline lens:(1) Preliminary report. American Journal of Ophthalmology, 25, 203–204.
10.1016/S0002-9394(42)92088-9 Google Scholar
- Hartnett, M.E. & Lane, R.H. (2013) Effects of oxygen on the development and severity of retinopathy of prematurity. Journal of AAPOS : The Official Publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus, 17, 229–234.
- Ashton, N., Ward, B. & Serpell, G. (1954) Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. British Journal of Ophthalmology, 38, 397–430.
- Hartnett, M.E. (2010) The effects of oxygen stresses on the development of features of severe retinopathy of prematurity: knowledge from the 50/10 OIR model. Documenta Ophthalmologica, 120, 25–39.
- Ward, J.P.T. (2008) Oxygen sensors in context. Biochimica et Biophysica Acta (BBA) – Bioenergetics, 1777, 1–14.
- Saito, Y., Geisen, P., Uppal, A. & Hartnett, M.E. (2007) Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity. Molecular Vision, 13, 840–853.
- Cunningham, S., Fleck, B.W., Elton, R.A. & Mclntosh, N. (1995) Transcutaneous oxygen levels in retinopathy of prematurity. Lancet, 346, 1464–1465.
- Hartnett, M.E. & Penn, J.S. (2012) Mechanisms and management of retinopathy of prematurity. New England Journal of Medicine, 367, 2515–2526.
- Hellstrom, A., Carlsson, B., Niklasson, A. et al. (2002) IGF-I is critical for normal vascularization of the human retina. Journal of Clinical Endocrinology Metabolism, 87, 3413–3416.
- Smith, L.E.H., Kopchick, J.J., Chen, W. et al. (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization. Science, 276, 1706–1709.
- Wang, H., Byfield, G., Jiang, Y., Smith, G.W., McCloskey, M. & Hartnett, M.E. (2012) VEGF-mediated STAT3 activation inhibits retinal vascularization by down-regulating local erythropoietin expression. American Journal of Pathology, 180, 1243–1253.
- Kermorvant-Duchemin, E., Sapieha, P., Sirinyan, M. et al. (2010) Understanding ischemic retinopathies: emerging concepts from oxygen-induced retinopathy. Documenta Ophthalmologica, 120, 51–60.
- Niesman, M.R., Johnson, K.A. & Penn, J.S. (1997) Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochemical Research, 22, 597–605.
- Penn, J.S., Madan, A., Caldwell, R.B., Bartoli, M., Caldwell, R.W. & Hartnett, M.E. (2008) Vascular endothelial growth factor in eye disease. Progress in Retinal and Eye Research, 27, 331–371.
- Patz, A. (1954) Oxygen studies in retrolental fibroplasia. American Journal of Ophthalmology, 38, 291–308.
- Di Fiore, J.M., Kaffashi, F., Loparo, K. et al. (2012) The relationship between patterns of intermittent hypoxia and retinopathy of prematurity in preterm infants. Pediatric Research, 72, 606–612.
- Group, T.S.-R.M.S. (2000) Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics, 105, 295–310.
- 2010) Early CPAP versus surfactant in extremely preterm infants. New England Journal of Medicine, 362, 1970–1979.
- Stenson, B.J., Tarnow-Mordi, W.O., Darlow, B.A. et al. (2013) Oxygen saturation and outcomes in preterm infants. New England Journal of Medicine, 368, 2094–2104.
- Schmidt, B., Whyte, R.K., Asztalos, E.V. et al. (2013) Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA, 309, 2111–2120.
- Owen, L. & Hartnett, M.E. (2014) Current concepts of oxygen management and ROP. Journal of Ophthalmic & Vision Research, 1, 94–100.
- Smith, L.E.H., Wesolowski, E., McLellan, A. et al. (1994) Oxygen induced retinopathy in the mouse. Investigative Ophthalmology & Visual Science, 35, 101–11.
- Penn, J.S., Tolman, B.L. & Lowery, L.A. (1993) Variable oxygen exposure causes preretinal neovascularization in the newborn rat. Investigative Ophthalmology & Visual Science, 34, 576–585.
- Wang, H., Smith, G.W., Yang, Z. et al. (2013) Short hairpin RNA-mediated knockdown of VEGFA in Muller cells reduces intravitreal neovascularization in a rat model of retinopathy of prematurity. American Journal of Pathology, 183, 964–74.
- McLeod, D.S., Brownstein, R. & Lutty, G.A. (1996) Vaso-obliteration in the canine model of oxygen-induced retinopathy. Investigative Ophthalmology & Visual Science, 37, 300–311.
- Ushio-Fukai, M. (2006) Redox signaling in angiogenesis: role of NADPH oxidase. Cardiovascular Research, 71, 226–235.
- Wilkinson-Berka, J.L., Rana, I., Armani, R. & Agrotis, A. (2013) Reactive oxygen species, Nox and angiotensin II in angiogenesis: implications for retinopathy. Clinical Science (London), 124, 597–615.
- Ushio-Fukai, M. & Nakamura, Y. (2008) Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Letters, 266, 37–52.
- Wang, H., Yang, Z., Jiang, Y. & Hartnett, M.E. (2014) Endothelial NADPH oxidase 4 mediates vascular endothelial growth factor receptor 2-induced intravitreal neovascularization in a rat model of retinopathy of prematurity. Molecular Vision, 20, 231–241.
- Saito, S., Shiozaki, A., Nakashima, A., Sakai, M. & Sasaki, Y. (2007) The role of the immune system in preeclampsia. Molecular Aspects of Medicine, 28, 192–209.
- Wilkinson-Berka, J., Deliyanti, D., Rana, I. et al. (2014) NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy. Antioxidants & Redox Signaling, 20, 2726–2740.
- Byfield, G., Budd, S. & Hartnett, M.E. (2009) The role of supplemental oxygen and JAK/STAT signaling in intravitreous neovascularization in a ROP rat model. Investigative Ophthalmology & Visual Science, 50, 3360–3365.
- Saito, Y., Uppal, A., Byfield, G., Budd, S. & Hartnett, M.E. (2008) Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model. Investigative Ophthalmology Visual Science, 49, 1591–1598.
- Wang, H., Byfield, G., Jiang, Y., Smith, G.W., McCloskey, M. & Hartnett, M.E. (2011) VEGF-mediated STAT3 activation inhibits retinal vascularization by downregulating erythropoietin expression. American Journal of Pathology, 2011, 180, 1243–53.
