1932

Abstract

Retinopathy of prematurity (ROP) is a complex disease involving development of the neural retina, ocular circulations, and other organ systems of the premature infant. The external stresses of the ex utero environment also influence the pathophysiology of ROP through interactions among retinal neural, vascular, and glial cells. There is variability among individual infants and presentations of the disease throughout the world, making ROP challenging to study. The methods used include representative animal models, cell culture, and clinical studies. This article describes the impact of maternal–fetal interactions; stresses that the preterm infant experiences; and biologic pathways of interest, including growth factor effects and cell–cell interactions, on the complex pathophysiology of ROP phenotypes in developed and emerging countries.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-vision-093022-021420
2023-09-15
2024-06-15
Loading full text...

Full text loading...

/deliver/fulltext/vision/9/1/annurev-vision-093022-021420.html?itemId=/content/journals/10.1146/annurev-vision-093022-021420&mimeType=html&fmt=ahah

Literature Cited

  1. Afzal A, Shaw LC, Caballero S, Spoerri PE, Lewin AS et al. 2003. Reduction in preretinal neovascularization by ribozymes that cleave the A2B adenosine receptor mRNA. Circ. Res. 93:500–6
    [Google Scholar]
  2. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD et al. 1994. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Eng. J. Med. 331:1480–87
    [Google Scholar]
  3. Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H et al. 1995. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. PNAS 92:10457–61
    [Google Scholar]
  4. Akula JD, Hansen RM, Tzekov R, Favazza TL, Vyhovsky TC et al. 2010. Visual cycle modulation in neurovascular retinopathy. Exp. Eye Res. 91:153–61
    [Google Scholar]
  5. Alon T, Hemo I, Itin A, Peer J, Stone J, Keshet E. 1995. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat. Med. 1:1024–28
    [Google Scholar]
  6. Alyamaç Sukgen E, Çömez A, Koçluk Y, Cevher S 2016. The process of retinal vascularization after anti-VEGF treatment in retinopathy of prematurity: a comparison study between ranibizumab and bevacizumab. Ophthalmologica 236:139–47
    [Google Scholar]
  7. Ashton N, Ward B, Serpell G. 1954. Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br. J. Ophthalmol. 38:397–430
    [Google Scholar]
  8. Bai Y, Ma JX, Guo J, Wang J, Zhu M et al. 2009. Müller cell-derived VEGF is a significant contributor to retinal neovascularization. J. Pathol. 219:446–54
    [Google Scholar]
  9. Banin E, Dorrell MI, Aguilar E, Ritter MR, Aderman CM et al. 2006. T2-TrpRS inhibits preretinal neovascularization and enhances physiological vascular regrowth in OIR as assessed by a new method of quantification. Investig. Ophthalmol. Vis. Sci. 47:2125–34
    [Google Scholar]
  10. Becker S, Wang H, Simmons AB, Suwanmanee T, Stoddard GJ et al. 2018. Targeted knockdown of overexpressed VEGFA or VEGF164 in Müller cells maintains retinal function by triggering different signaling mechanisms. Sci. Rep. 8:2003
    [Google Scholar]
  11. Becker S, Wang H, Yu B, Brown R, Han X et al. 2017. Protective effect of maternal uteroplacental insufficiency on oxygen-induced retinopathy in offspring: removing bias of premature birth. Sci. Rep. 7:42301
    [Google Scholar]
  12. Berkowitz BA, Zhang W. 2000. Significant reduction of the panretinal oxygenation response after 28% supplemental oxygen recovery in experimental ROP. Investig. Ophthalmol. Vis. Sci. 41:1925–31
    [Google Scholar]
  13. Blanco R, Gerhardt H. 2013. VEGF and Notch in tip and stalk cell selection. Cold Spring Harb. Perspect. Med. 3:a006569
    [Google Scholar]
  14. Blencowe H, Lawn JE, Vazquez T, Fielder A, Gilbert C. 2013. Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatr. Res. 74:Suppl. 135–49
    [Google Scholar]
  15. Bretz CA, Divoky V, Prchal J, Kunz E, Simmons AB et al. 2018. Erythropoietin signaling increases choroidal macrophages and cytokine expression, and exacerbates choroidal neovascularization. Sci. Rep. 8:2161
    [Google Scholar]
  16. Bretz CA, Ramshekar A, Kunz E, Wang H, Hartnett ME. 2020a. Signaling through the erythropoietin receptor affects angiogenesis in retinovascular disease. Investig. Ophthalmol. Vis. Sci. 61:23
    [Google Scholar]
  17. Bretz CA, Simmons AB, Kunz E, Ramshekar A, Kennedy C et al. 2020b. Erythropoietin receptor signaling supports retinal function after vascular injury. Am. J. Pathol. 190:630–41
    [Google Scholar]
  18. Brines M, Cerami A. 2006. Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise. Kidney Int. 70:246–50
    [Google Scholar]
  19. Budd SJ, Hartnett ME. 2010. Increased angiogenic factors associated with peripheral avascular retina and intravitreous neovascularization: a model of retinopathy of prematurity. Arch. Ophthalmol. 128:589–95
    [Google Scholar]
  20. Budd SJ, Thompson H, Hartnett ME. 2010. Association of retinal vascular endothelial growth factor with avascular retina in a rat model of retinopathy of prematurity. Arch. Ophthalmol. 128:1014–21
    [Google Scholar]
  21. Bujold E, Romero R, Chaiworapongsa T, Kim YM, Kim GJ et al. 2005. Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin. J. Matern. Fetal Neonatal Med. 18:9–16
    [Google Scholar]
  22. Byfield G, Budd S, Hartnett ME. 2009. The role of supplemental oxygen and JAK/STAT signaling in intravitreous neovascularization in a ROP rat model. Investig. Ophthalmol. Vis. Sci. 50:3360–65
    [Google Scholar]
  23. Campbell K. 1951. Intensive oxygen therapy as a possible cause of retrolental fibroplasia. A clinical approach. Med. J. Aust. 2:48–50
    [Google Scholar]
  24. Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG et al. 2010. Target ranges of oxygen saturation in extremely preterm infants. N. Engl. J. Med. 362:1959–69
    [Google Scholar]
  25. Chan PY, Tang SM, Au SC, Rong SS, Lau HH et al. 2016. Association of gestational hypertensive disorders with retinopathy of prematurity: a systematic review and meta-analysis. Sci. Rep. 6:30732
    [Google Scholar]
  26. Chang E, Josan AS, Purohit R, Patel CK, Xue K. 2022. A network meta-analysis of retreatment rates following bevacizumab, ranibizumab, aflibercept, and laser for retinopathy of prematurity. Ophthalmology 129:1389–401
    [Google Scholar]
  27. Chan-Ling T, Gock B, Stone J. 1995. The effect of oxygen on vasoformative cell division: evidence that “physiological hypoxia” is the stimulus for normal retinal vasculogenesis. Investig. Ophthalmol. Vis. Sci. 36:1201–14
    [Google Scholar]
  28. Chan-Ling T, McLeod DS, Hughes S, Baxter L, Chu Y et al. 2004. Astrocyte-endothelial cell relationships during human retinal vascular development. Investig. Ophthalmol. Vis. Sci. 45:2020–32
    [Google Scholar]
  29. Chen DY, Sun NH, Chen X, Gong JJ, Yuan ST et al. 2021. Endothelium-derived semaphorin 3G attenuates ischemic retinopathy by coordinating β-catenin-dependent vascular remodeling. J. Clin. Investig. 131:e135296
    [Google Scholar]
  30. Chen J, Connor KM, Aderman CM, Smith LE. 2008. Erythropoietin deficiency decreases vascular stability in mice. J. Clin. Investig. 118:526–33
    [Google Scholar]
  31. Chen J, Connor KM, Aderman CM, Willett KL, Aspegren OP, Smith LEH. 2009. Suppression of retinal neovascularization by erythropoietin siRNA in a mouse model of proliferative retinopathy. Investig. Ophthalmol. Vis. Sci. 50:1329–35
    [Google Scholar]
  32. Chen ML, Allred EN, Hecht JL, Onderdonk A, Vanderveen D et al. 2011. Placenta microbiology and histology and the risk for severe retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 52:7052–58
    [Google Scholar]
  33. Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Chan RVP et al. 2021. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology 128:e51–68
    [Google Scholar]
  34. Chidiac R, Abedin M, MacLeod G, Yang A, Thibeault PE et al. 2021. A Norrin/Wnt surrogate antibody stimulates endothelial cell barrier function and rescues retinopathy. EMBO Mol. Med. 13:e13977
    [Google Scholar]
  35. Connor KM, Sangiovanni JP, Lofqvist C, Aderman CM, Chen J et al. 2007. Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat. Med. 13:868–73
    [Google Scholar]
  36. Cota F, Costa S, Giannantonio C, Purcaro V, Catenazzi P, Vento G. 2022. Lutein supplementation and retinopathy of prematurity: a meta-analysis. J. Matern. Fetal Neonatal Med. 35:175–80
    [Google Scholar]
  37. Crespo-Garcia S, Tsuruda PR, Dejda A, Ryan RD, Fournier F et al. 2021. Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition. Cell Metab. 33:818–32.e7
    [Google Scholar]
  38. Cryother. Retin. Prematur. Coop 2001. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity: ophthalmological outcomes at 10 years. Arch. Ophthalmol. 119:1110–18
    [Google Scholar]
  39. Cudjoe GA, Ameley A, Ohemeng-Dapaah J, Bhatt P, Donda K, Dapaah-Siakwan F. 2022. National trends in the incidence and management of retinopathy of prematurity in the United States, 2009–2018. J. Neonatal Perinatal Med. 15:553–57
    [Google Scholar]
  40. Cung T, Wang H, Hartnett ME. 2022. The effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and erythropoietin, and their interactions in angiogenesis: implications in retinopathy of prematurity. Cells 11:1951
    [Google Scholar]
  41. Cunningham S, Fleck BW, Elton RA, McIntosh N. 1995. Transcutaneous oxygen levels in retinopathy of prematurity. Lancet 346:1464–65
    [Google Scholar]
  42. Cunningham S, McColm JR, Wade J, Sedowofia K, McIntosh N, Fleck B. 2000. A novel model of retinopathy of prematurity simulating preterm oxygen variability in the rat. Investig. Ophthalmol. Vis. Sci. 41:4275–80
    [Google Scholar]
  43. Dai C, Tian H, Bhatt A, Su G, Webster KA, Li W. 2022. Safety and efficacy of systemic anti-Scg3 therapy to treat oxygen-induced retinopathy. Front. Biosci. 27:130
    [Google Scholar]
  44. Dalvin LA, Hartnett ME, Bretz CA, Hann CR, Cui RZ et al. 2019. Stanniocalcin-1 is a modifier of oxygen-induced retinopathy severity. Curr. Eye Res. 45:46–51
    [Google Scholar]
  45. Dammann O, Hartnett ME, Stahl A. 2023. Retinopathy of prematurity. Dev. Med. Child Neurol. 65:5625–31
    [Google Scholar]
  46. Darlow BA, Gilbert CE, Quiroga AM. 2013. Setting up and improving retinopathy of prematurity programs: interaction of neonatology, nursing, and ophthalmology. Clin. Perinatol. 40:215–27
    [Google Scholar]
  47. Dhaliwal CA, Wade J, Gillespie T, Aspinall P, McIntosh N, Fleck BW. 2011. Early retinal blood vessel growth in normal and growth restricted rat pups raised in oxygen and room air. Br. J. Ophthalmol. 95:1592–96
    [Google Scholar]
  48. Di Fiore JM, MacFarlane PM, Martin RJ. 2019. Intermittent hypoxemia in preterm infants. Clin. Perinatol. 46:553–65
    [Google Scholar]
  49. Dorrell MI, Aguilar E, Friedlander M. 2002. Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion. Investig. Ophthalmol. Vis. Sci. 43:3500–10
    [Google Scholar]
  50. Dou GR, Wang L, Wang YS, Han H. 2012. Notch signaling in ocular vasculature development and diseases. Mol. Med. 18:47–55
    [Google Scholar]
  51. Elliott S, Busse L, Bass MB, Lu H, Sarosi I et al. 2006. Anti-Epo receptor antibodies do not predict Epo receptor expression. Blood 107:1892–95
    [Google Scholar]
  52. Elliott S, Busse L, McCaffery I, Rossi J, Sinclair A et al. 2010. Identification of a sensitive anti-erythropoietin receptor monoclonal antibody allows detection of low levels of EpoR in cells. J. Immunol. Methods 352:126–39
    [Google Scholar]
  53. Ferrara N. 2009. Vascular endothelial growth factor. Arterioscler. Thromb. Vasc. Biol. 29:789–91
    [Google Scholar]
  54. Fevereiro-Martins M, Guimarães H, Marques-Neves C, Bicho M. 2022. Retinopathy of prematurity: contribution of inflammatory and genetic factors. Mol. Cell Biochem. 477:1739–63
    [Google Scholar]
  55. Fidler M, Fleck BW, Stahl A, Marlow N, Chastain JE et al. 2020. Ranibizumab population pharmacokinetics and free VEGF pharmacodynamics in preterm infants with retinopathy of prematurity in the RAINBOW trial. Transl. Vis. Sci. Technol. 9:43
    [Google Scholar]
  56. Fierson WM. 2018. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 142:e20183061
    [Google Scholar]
  57. Finkel T. 2011. Signal transduction by reactive oxygen species. J. Cell Biol. 194:7–15
    [Google Scholar]
  58. Fliesler SJ, Anderson RE. 1983. Chemistry and metabolism of lipids in the vertebrate retina. Prog. Lipid Res. 22:79–131
    [Google Scholar]
  59. Fortes Filho JB, Costa MC, Eckert GU, Santos PG, Silveira RC, Procianoy RS 2011. Maternal preeclampsia protects preterm infants against severe retinopathy of prematurity. J. Pediatr. 158:372–76
    [Google Scholar]
  60. Freedman SF, Hercinovic A, Wallace DK, Kraker RT, Li Z et al. 2022. Low- and very low-dose bevacizumab for retinopathy of prematurity: reactivations, additional treatments, and 12-month outcomes. Ophthalmology 129:1120–28
    [Google Scholar]
  61. Fukushima Y, Okada M, Kataoka H, Hirashima M, Yoshida Y et al. 2011. Sema3E-PlexinD1 signaling selectively suppresses disoriented angiogenesis in ischemic retinopathy in mice. J. Clin. Investig. 121:1974–85
    [Google Scholar]
  62. Fulton AB, Hansen RM, Moskowitz A, Akula JD. 2009. The neurovascular retina in retinopathy of prematurity. Prog. Retin. Eye Res. 28:452–82
    [Google Scholar]
  63. Fung C, Brown A, Cox J, Callaway C, McKnight R, Lane R. 2011. Novel thromboxane A2 analog-induced IUGR mouse model. J. Dev. Orig. Health Dis. 2:291–301
    [Google Scholar]
  64. Fung C, Cung T, Nelson C, Wang H, Bretz C et al. 2023. Retinopathy of prematurity protection conferred by uteroplacental insufficiency through erythropoietin signaling in an experimental murine model. Pediatr. Res. In press
    [Google Scholar]
  65. Gagliardi L, Rusconi F, Da Fre M, Mello G, Carnielli V et al. 2013. Pregnancy disorders leading to very preterm birth influence neonatal outcomes: results of the population-based ACTION cohort study. Pediatr. Res. 73:794–801
    [Google Scholar]
  66. Gariano RF. 2003. Cellular mechanisms in retinal vascular development. Prog. Retin. Eye Res. 22:295–306
    [Google Scholar]
  67. Gaynon MW, Wong RJ, Stevenson DK, Sunshine P. 2018. Prethreshold retinopathy of prematurity: VEGF inhibition without VEGF inhibitors. J. Perinatol. 38:1295–300
    [Google Scholar]
  68. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A et al. 2003. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J. Cell Biol. 161:1163–77
    [Google Scholar]
  69. Gilbert C, Malik ANJ, Nahar N, Das SK, Visser L et al. 2019. Epidemiology of ROP update—Africa is the new frontier. Semin. Perinatol. 43:317–22
    [Google Scholar]
  70. Gilbert CE, Lepvrier-Chomette N. 2021. Education and management of retinopathy of prematurity worldwide. Pediatric Retina ME Hartnett 763–84. Philadelphia: Lippincott Williams & Wilkins. , 3rd ed..
    [Google Scholar]
  71. Han X, Kong J, Hartnett ME, Wang H. 2019. Enhancing retinal endothelial glycolysis by inhibiting UCP2 promotes physiologic retinal vascular development in a model of retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 60:1604–13
    [Google Scholar]
  72. Hardy RJ, Palmer EA, Dobson V, Summers CG, Phelps DL et al. 2003. Risk analysis of prethreshold retinopathy of prematurity. Arch. Ophthalmol. 121:1697–701
    [Google Scholar]
  73. Hartmann JS, Thompson H, Wang H, Kaneka S, Huang W et al. 2011. Expression of vascular endothelial growth factor and pigment epithelial-derived factor in a rat model of retinopathy of prematurity. Mol. Vis. 17:1577–87
    [Google Scholar]
  74. Hartnett ME. 2010a. The effects of oxygen stresses on the development of features of severe retinopathy of prematurity: knowledge from the 50/10 OIR model. Doc. Ophthalmol. 120:25–39
    [Google Scholar]
  75. Hartnett ME. 2010b. Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an American Ophthalmological Society thesis). Trans. Am. Ophthalmol. Soc. 108:96–119
    [Google Scholar]
  76. Hartnett ME, Deangelis MM. 2012. Studies on retinal and choroidal disorders. Studies on Retinal and Choroidal Disorders D Armstrong 559–84. New York: Humana Press. , 1st ed..
    [Google Scholar]
  77. Hartnett ME, Martiniuk D, Byfield G, Geisen P, Zeng G, Bautch VL. 2008. Neutralizing VEGF decreases tortuosity and alters endothelial cell division orientation in arterioles and veins in a rat model of ROP: relevance to plus disease. Investig. Ophthalmol. Vis. Sci. 49:3107–14
    [Google Scholar]
  78. Hartnett ME, Morrison MA, Smith S, Yanovitch TL, Young TL et al. 2014. Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants. Investig. Ophthalmol. Vis. Sci. 55:6194–203
    [Google Scholar]
  79. Hartnett ME, Penn JS. 2012. Mechanisms and management of retinopathy of prematurity. N. Engl. J. Med. 367:2515–26
    [Google Scholar]
  80. Hartnett ME, Wallace DK. 2022. Plasma levels of vascular endothelial growth factor after low-dose bevacizumab treatment for retinopathy of prematurity study—more questions than answers?—Reply. JAMA Ophthalmol. 140:911–12
    [Google Scholar]
  81. Hartnett ME, Wallace DK, Dean TW, Li Z, Boente CS et al. 2022. Plasma levels of bevacizumab and vascular endothelial growth factor after low-dose bevacizumab treatment for retinopathy of prematurity in infants. JAMA Ophthalmol. 140:337–44
    [Google Scholar]
  82. Hellgren G, Löfqvist C, Hård AL, Hansen-Pupp I, Gram M et al. 2016. Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity. Pediatr. Res. 79:70–75
    [Google Scholar]
  83. Hellström A, Engstrom E, Hard A-L, Albertsson-Wickland K, Carlsson B et al. 2003. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics 112:1016–20
    [Google Scholar]
  84. Hellström A, Nilsson AK, Wackernagel D, Pivodic A, Vanpee M et al. 2021a. Effect of enteral lipid supplement on severe retinopathy of prematurity: a randomized clinical trial. JAMA Pediatr. 175:359–67
    [Google Scholar]
  85. Hellström A, Perruzzi C, Ju M, Engstrom E, Hard AL et al. 2001. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. PNAS 98:5804–8
    [Google Scholar]
  86. Hellström M, Phng LK, Hofmann JJ, Wallgard E, Coultas L et al. 2007. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445:776–80
    [Google Scholar]
  87. Hellström A, Pivodic A, Gränse L, Lundgren P, Sjöbom U et al. 2021b. Association of docosahexaenoic acid and arachidonic acid serum levels with retinopathy of prematurity in preterm infants. JAMA Netw. Open 4:e2128771
    [Google Scholar]
  88. Hendrickson AE, Yuodelis C. 1984. The morphological development of the human fovea. Ophthalmology 91:603–12
    [Google Scholar]
  89. Holm M, Morken TS, Fichorova RN, Vanderveen DK, Allred EN et al. 2017. Systemic inflammation-associated proteins and retinopathy of prematurity in infants born before the 28th week of gestation. Investig. Ophthalmol. Vis. Sci. 58:6419–28
    [Google Scholar]
  90. Holmes JM, Duffner LA. 1996. The effect of postnatal growth retardation on abnormal neovascularization in the oxygen exposed neonatal rat. Curr. Eye Res. 15:403–9
    [Google Scholar]
  91. Hong HK, Lee HJ, Ko JH, Park JH, Park JY et al. 2014. Neonatal systemic inflammation in rats alters retinal vessel development and simulates pathologic features of retinopathy of prematurity. J. Neuroinflamm. 11:87
    [Google Scholar]
  92. Hoppe G, Yoon S, Gopalan B, Savage AR, Brown R et al. 2016. Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity. PNAS 113:E2516–25
    [Google Scholar]
  93. Hu J. 2012. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch. Opthalmol. 130:1000–6
    [Google Scholar]
  94. Hu J, Bibli SI, Wittig J, Zukunft S, Lin J et al. 2019. Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity. J. Clin. Investig. 129:5204–18
    [Google Scholar]
  95. Hughes S, Yang H, Chan-Ling T. 2000. Vascularisation of the human fetal retina: roles of vasculogenesis and angiogenesis. Investig. Ophthalmol. Vis. Sci. 41:1217–28
    [Google Scholar]
  96. Ishida S, Usui T, Yamashiro K, Kaji Y, Amano S et al. 2003. VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J. Exp. Med. 198:483–89
    [Google Scholar]
  97. Ji MH, Moshfeghi DM, Shields RA, Bodnar Z, Ludwig CA et al. 2021. Conserved regression patterns of retinopathy of prematurity after intravitreal ranibizumab: a class effect. Eur. J. Ophthalmol. 31:2135–40
    [Google Scholar]
  98. Joyal JS, Sitaras N, Binet F, Rivera JC, Stahl A et al. 2011. Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A. Blood 117:6024–35
    [Google Scholar]
  99. Juul SE, Comstock BA, Wadhawan R, Mayock DE, Courtney SE et al. 2020. A randomized trial of erythropoietin for neuroprotection in preterm infants. N. Engl. J. Med. 382:233–43
    [Google Scholar]
  100. Juul SE, Mayock DE, Comstock BA, Heagerty PJ. 2015. Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern. Health Neonatol. Perinatol. 1:27
    [Google Scholar]
  101. Karaman S, Leppänen VM, Alitalo K. 2018. Vascular endothelial growth factor signaling in development and disease. Development 145:dev151019
    [Google Scholar]
  102. Karumanchi SA, Maynard SE, Stillman IE, Epstein FH, Sukhatme VP. 2005. Preeclampsia: a renal perspective. Kidney Int. 67:2101–13
    [Google Scholar]
  103. Kim SJ, Sonmez K, Swan R, Campbell JP, Ostmo S et al. 2021. Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes. Sci. Rep. 11:4966
    [Google Scholar]
  104. Kingsley DM, Rinchik EM, Russell LB, Ottiger HP, Sutcliffe JG et al. 1990. Genetic ablation of a mouse gene expressed specifically in brain. EMBO J. 9:395–99
    [Google Scholar]
  105. Kinsey VE, Arnold HJ, Kalina RE, Stern L, Stahlman M et al. 1977. PaO2 levels and retrolental fibroplasia: a report of the cooperative study. Pediatrics 60:655–68
    [Google Scholar]
  106. Kong L, Bhatt AR, Demny AB, Coats DK, Li A et al. 2015. Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 56:956–61
    [Google Scholar]
  107. Lee S, Elaskandrany M, Lau LF, Lazzaro D, Grant MB, Chaqour B. 2017. Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy. Sci. Rep. 7:1405
    [Google Scholar]
  108. Lepore D, Molle F, Pagliara MM, Baldascino A, Angora C et al. 2011. Atlas of fluorescein angiographic findings in eyes undergoing laser for retinopathy of prematurity. Ophthalmology 118:168–75
    [Google Scholar]
  109. Ley D, Hallberg B, Hansen-Pupp I, Dani C, Ramenghi LA et al. 2019. rhIGF-1/rhIGFBP-3 in preterm infants: a phase 2 randomized controlled trial. J. Pediatr. 206:56–65.e8
    [Google Scholar]
  110. Li Calzi S, Shaw LC, Moldovan L, Shelley WC, Qi X et al. 2019. Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model. JCI Insight 4:e129224
    [Google Scholar]
  111. Lundgren P, Hellgren G, Pivodic A, Savman K, Smith LEH, Hellström A. 2019. Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity. Pediatr. Res. 86:276–82
    [Google Scholar]
  112. Lutty GA, McLeod DS. 2018. Development of the hyaloid, choroidal and retinal vasculatures in the fetal human eye. Prog. Retin. Eye Res. 62:58–76
    [Google Scholar]
  113. Lutty GA, McLeod DS, Bhutto I, Wiegand SJ. 2011. Effect of VEGF trap on normal retinal vascular development and oxygen-induced retinopathy in the dog. Investig. Ophthalmol. Vis. Sci. 52:4039–47
    [Google Scholar]
  114. Manja V, Saugstad OD, Lakshminrusimha S. 2017. Oxygen saturation targets in preterm infants and outcomes at 18–24 months: a systematic review. Pediatrics 139:e20161609
    [Google Scholar]
  115. Mann I. 1964. The Development of the Human Eye New York: Grune & Stratton. , 3rd ed..
    [Google Scholar]
  116. McCloskey M, Wang H, Jiang Y, Smith GW, Strange J, Hartnett ME. 2013. Anti-VEGF antibody leads to later atypical intravitreous neovascularization and activation of angiogenic pathways in a rat model of retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 54:2020–26
    [Google Scholar]
  117. McColm JR, Cunningham S, Wade J, Sedowofia K, Gellen B et al. 2004a. Hypoxic oxygen fluctuations produce less severe retinopathy than hyperoxic fluctuations in a rat model of retinopathy of prematurity. Pediatr. Res. 55:107–13
    [Google Scholar]
  118. McColm JR, Geisen P, Hartnett ME. 2004b. VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP. Mol. Vis. 10:512–20
    [Google Scholar]
  119. McLeod DS, Brownstein R, Lutty GA. 1996a. Vaso-obliteration in the canine model of oxygen-induced retinopathy. Investig. Ophthalmol. Vis. Sci. 37:300–11
    [Google Scholar]
  120. McLeod DS, Crone SN, Lutty GA. 1996b. Vasoproliferation in the neonatal dog model of oxygen-induced retinopathy. Investig. Ophthalmol. Vis. Sci. 37:1322–33
    [Google Scholar]
  121. McLeod DS, Lutty GA. 2016. Targeting VEGF in canine oxygen-induced retinopathy—a model for human retinopathy of prematurity. Eye Brain 8:55–65
    [Google Scholar]
  122. Mechoulam H, Pierce EA. 2005. Expression and activation of STAT3 in ischemia-induced retinopathy. Investig. Ophthalmol. Vis. Sci. 46:4409–16
    [Google Scholar]
  123. Mintz-Hittner HA, Kennedy KA, Chuang AZ, BEAT-ROP Coop. Group 2011. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N. Engl. J. Med. 364:603–15
    [Google Scholar]
  124. Morin J, Luu TM, Superstein R, Ospina LH, Lefebvre F et al. 2016. Neurodevelopmental outcomes following bevacizumab injections for retinopathy of prematurity. Pediatrics 137:e20153218
    [Google Scholar]
  125. Natarajan G, Shankaran S, Nolen TL, Sridhar A, Kennedy KA et al. 2019. Neurodevelopmental outcomes of preterm infants with retinopathy of prematurity by treatment. Pediatrics 144:e20183537
    [Google Scholar]
  126. Nguyen MT, Vemaraju S, Nayak G, Odaka Y, Buhr ED et al. 2019. An opsin 5-dopamine pathway mediates light-dependent vascular development in the eye. Nat. Cell Biol. 21:420–29
    [Google Scholar]
  127. Niesman MR, Johnson KA, Penn JS. 1997. Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochem. Res. 22:597–605
    [Google Scholar]
  128. Noueihed B, Rivera JC, Dabouz R, Abram P, Omri S et al. 2021. Mesenchymal stromal cells promote retinal vascular repair by modulating Sema3E and IL-17A in a model of ischemic retinopathy. Front. Cell Dev. Biol. 9:630645
    [Google Scholar]
  129. Ohlmann A, Scholz M, Goldwich A, Chauhan BK, Hudl K et al. 2005. Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice. J. Neurosci. 25:1701–10
    [Google Scholar]
  130. Ohlmann A, Tamm ER. 2012. Norrin: molecular and functional properties of an angiogenic and neuroprotective growth factor. Prog. Retin. Eye Res. 31:243–57
    [Google Scholar]
  131. Ohls RK, Kamath-Rayne BD, Christensen RD, Wiedmeier SE, Rosenberg A et al. 2014. Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo. Pediatrics 133:1023–30
    [Google Scholar]
  132. Okawa H, Sampath AP, Laughlin SB, Fain GL. 2008. ATP consumption by mammalian rod photoreceptors in darkness and in light. Curr. Biol. 18:1917–21
    [Google Scholar]
  133. Oubaha M, Miloudi K, Dejda A, Guber V, Mawambo G et al. 2016. Senescence-associated secretory phenotype contributes to pathological angiogenesis in retinopathy. Sci. Transl. Med. 8:362ra144
    [Google Scholar]
  134. Owen L, Hartnett ME. 2014. Current concepts of oxygen management in retinopathy of prematurity. J. Ophthalmic Vis. Res. 9:94–100
    [Google Scholar]
  135. Owen LA, Shirer K, Collazo SA, Szczotka K, Baker S et al. 2020. The serine protease HTRA-1 is a biomarker for ROP and mediates retinal neovascularization. Front. Mol. Neurosci. 13:605918
    [Google Scholar]
  136. Patz A, Hoeck LE, De La Cruz E. 1952. Studies on the effect of high oxygen administration in retrolental fibroplasia. I. Nursery observations. Am. J. Ophthalmol. 35:1248–53
    [Google Scholar]
  137. Payne LB, Zhao H, James CC, Darden J, McGuire D et al. 2019. The pericyte microenvironment during vascular development. Microcirculation 26:e12554
    [Google Scholar]
  138. Penn JS, Tolman BL, Lowery LA. 1993. Variable oxygen exposure causes preretinal neovascularisation in the newborn rat. Investig. Ophthalmol. Vis. Sci. 34:576–85
    [Google Scholar]
  139. Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LEH. 1995. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. PNAS 92:905–9
    [Google Scholar]
  140. Provis JM. 2001. Development of the primate retinal vasculature. Prog. Retin. Eye Res. 20:799–821
    [Google Scholar]
  141. Provis JM, Hendrickson AE. 2008. The foveal avascular region of developing human retina. Arch. Ophthalmol. 126:507–11
    [Google Scholar]
  142. Provis JM, Leech J, Diaz CM, Penfold PL, Stone J, Keshet E. 1997. Development of the human retinal vasculature: cellular relations and VEGF expression. Exp. Eye Res. 65:555–68
    [Google Scholar]
  143. Quinn GE. 2016. Retinopathy of prematurity blindness worldwide: phenotypes in the third epidemic. Eye Brain 8:31–36
    [Google Scholar]
  144. Ramshekar A, Bretz CA, Hartnett ME. 2022. RNA-seq provides insights into VEGF-induced signaling in human retinal microvascular endothelial cells: implications in retinopathy of prematurity. Int. J. Mol. Sci. 23:7354
    [Google Scholar]
  145. Ramshekar A, Hartnett ME. 2021. Vascular endothelial growth factor signaling in models of oxygen-induced retinopathy: insights into mechanisms of pathology in retinopathy of prematurity. Front. Pediatr. 9:796143
    [Google Scholar]
  146. Rao S, Chun C, Fan J, Kofron JM, Yang MB et al. 2013. A direct and melanopsin-dependent fetal light response regulates mouse eye development. Nature 494:243–46
    [Google Scholar]
  147. Reynolds JD, Hardy RJ, Kennedy KA, Spencer R, Van Heuven WAJ, Fielder AR. 1998. Lack of efficacy of light reduction in preventing retinopathy of prematurity. N. Engl. J. Med. 338:1572–76
    [Google Scholar]
  148. Rivera JC, Sitaras N, Noueihed B, Hamel D, Madaan A et al. 2013. Microglia and interleukin-1β in ischemic retinopathy elicit microvascular degeneration through neuronal semaphorin-3A. Arterioscler. Thromb. Vasc. Biol. 33:1881–91
    [Google Scholar]
  149. Saito Y, Uppal A, Byfield G, Budd S, Hartnett M. 2007. Inhibition of NAD(P)H oxidase activity reduces intra-vitreous neovascularization caused by supplemental oxygen in a rat model of retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 13:840–53
    [Google Scholar]
  150. Saito Y, Uppal A, Byfield G, Budd S, Hartnett ME. 2008. Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model. Investig. Ophthalmol. Vis. Sci. 49:1591–98
    [Google Scholar]
  151. Sapieha P, Sirinyan M, Hamel D, Zaniolo K, Joyal JS et al. 2008. The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis. Nat. Med. 14:1067–76
    [Google Scholar]
  152. Sayah DN, Zhou TE, Omri S, Mazzaferri J, Quiniou C et al. 2020. Novel anti-interleukin-1β therapy preserves retinal integrity: a longitudinal investigation using OCT imaging and automated retinal segmentation in small rodents. Front. Pharmacol. 11:296
    [Google Scholar]
  153. Schaffer DB, Palmer EA, Plotsky DF, Metz HS, Flynn JT et al. 1993. Prognostic factors in the natural course of retinopathy of prematurity. Ophthalmology 100:230–37
    [Google Scholar]
  154. Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C et al. 2013. Effects of targeting higher versus lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. J. Am. Med. Assoc. 309:2111–20
    [Google Scholar]
  155. Sears JE, Hoppe G, Ebrahem Q, Anand-Apte B. 2008. Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy. PNAS 105:19898–903
    [Google Scholar]
  156. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. 1983. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–85
    [Google Scholar]
  157. Shen J, Xiao R, Bair J, Wang F, Vandenberghe LH et al. 2018. Novel engineered, membrane-localized variants of vascular endothelial growth factor (VEGF) protect retinal ganglion cells: a proof-of-concept study. Cell Death Dis. 9:1018
    [Google Scholar]
  158. Shosha E, Xu Z, Yokota H, Saul A, Rojas M et al. 2016. Arginase 2 promotes neurovascular degeneration during ischemia/reperfusion injury. Cell Death Dis. 7:e2483
    [Google Scholar]
  159. Shulman JP, Weng C, Wilkes J, Greene T, Hartnett ME. 2017. Association of maternal preeclampsia with infant risk of premature birth and retinopathy of prematurity. JAMA Ophthalmol. 135:947–53
    [Google Scholar]
  160. Simmons AB, Bretz CA, Wang H, Kunz E, Hajj K et al. 2018. Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy. Angiogenesis 21:751–64
    [Google Scholar]
  161. Smith LEH, Kopchick JJ, Chen W, Knapp J, Kinose F et al. 1997. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276:1706–9
    [Google Scholar]
  162. Smith LEH, Wesolowski E, McLellan A, Kostyk SK, D'Amato R et al. 1994. Oxygen induced retinopathy in the mouse. Investig. Ophthalmol. Vis. Sci. 35:101–11
    [Google Scholar]
  163. Soghier LM, Brion LP. 2006. Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates. Cochrane Database Syst. Rev. 2006:CD004869
    [Google Scholar]
  164. Stahl A, Lepore D, Fielder A, Fleck B, Reynolds JD et al. 2019. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet 394:1551–59
    [Google Scholar]
  165. Stahl A, Sukgen EA, Wu WC, Lepore D, Nakanishi H et al. 2022. Effect of intravitreal aflibercept versus laser photocoagulation on treatment success of retinopathy of prematurity: the FIREFLEYE randomized clinical trial. J. Am. Med. Assoc. 328:348–59
    [Google Scholar]
  166. Stenson BJ, Tarnow-Mordi WO, Darlow BA, Simes J, Juszczak E et al. 2013. Oxygen saturation and outcomes in preterm infants. N. Engl. J. Med. 368:2094–104
    [Google Scholar]
  167. Stoltz Sjöström E, Lundgren P, Öhlund I, Holmström G, Hellström A, Domellöf M 2016. Low energy intake during the first 4 weeks of life increases the risk for severe retinopathy of prematurity in extremely preterm infants. Arch. Dis. Child Fetal Neonatal Ed. 101:F108–13
    [Google Scholar]
  168. Stone J, Itin A, Alon T, Peer J, Gnessin H et al. 1995. Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J. Neurosci. 15:4738–47
    [Google Scholar]
  169. STOP-ROP Multicent. Study Group 2000. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized, controlled trial. I: Primary outcomes. Pediatrics 105:295–310
    [Google Scholar]
  170. Stuttfeld E, Ballmer-Hofer K. 2009. Structure and function of VEGF receptors. IUBMB Life 61:915–22
    [Google Scholar]
  171. Sun Y, Liu CH, Wang Z, Meng SS, Burnim SB et al. 2017. RORα modulates semaphorin 3E transcription and neurovascular interaction in pathological retinal angiogenesis. FASEB J. 31:4492–502
    [Google Scholar]
  172. Terry TL. 1942. Extreme prematurity and fibroblastic overgrowth of persistent vascular sheath behind each crystalline lens: 1. Preliminary report. Am. J. Ophthalmol. 25:203–4
    [Google Scholar]
  173. Tremblay S, Miloudi K, Chaychi S, Favret S, Binet F et al. 2013. Systemic inflammation perturbs developmental retinal angiogenesis and neuroretinal function. Investig. Ophthalmol. Vis. Sci. 54:8125–39
    [Google Scholar]
  174. Wallace DK, Kraker RT, Freedman SF, Crouch ER, Hutchinson AK et al. 2017. Assessment of lower doses of intravitreous bevacizumab for retinopathy of prematurity: a phase 1 dosing study. JAMA Ophthalmol. 135:654–56
    [Google Scholar]
  175. Wallace DK, Kylstra JA, Phillips SJ, Hall JG. 2000. Poor postnatal weight gain: a risk factor for severe retinopathy of prematurity. J. AAPOS 4:343–47
    [Google Scholar]
  176. Walsh MC, Di Fiore JM, Martin RJ, Gantz M, Carlo WA, Finer N. 2016. Association of oxygen target and growth status with increased mortality in small for gestational age infants: further analysis of the surfactant, positive pressure and pulse oximetry randomized trial. JAMA Pediatr. 170:292–94
    [Google Scholar]
  177. Wang H, Smith GW, Yang Z, Jiang Y, McCloskey M et al. 2013a. Short hairpin RNA-mediated knockdown of VEGFA in Müller cells reduces intravitreal neovascularization in a rat model of retinopathy of prematurity. Am. J. Pathol. 183:964–74
    [Google Scholar]
  178. Wang H, Yang Z, Jiang Y, Flannery J, Hammond S et al. 2014. Quantitative analyses of retinal vascular area and density after different methods to reduce VEGF in a rat model of retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 55:737–44
    [Google Scholar]
  179. Wang H, Zhang SX, Hartnett ME. 2013b. Signaling pathways triggered by oxidative stress that mediate features of severe retinopathy of prematurity. JAMA Ophthalmol. 131:80–85
    [Google Scholar]
  180. Wei Y, Gong J, Xu Z, Thimmulappa RK, Mitchell KL et al. 2015. Nrf2 in ischemic neurons promotes retinal vascular regeneration through regulation of semaphorin 6A. PNAS 112:E6927–36
    [Google Scholar]
  181. Weiner GA, Shah SH, Angelopoulos CM, Bartakova AB, Pulido RS et al. 2019. Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation. Nat. Commun. 10:2477
    [Google Scholar]
  182. Weiter JJ, Zuckerman R, Schepens CL. 1982. A model for the pathogenesis of retrolental fibroplasia based on the metabolic control of blood vessel development. Ophthalmic Surg. 12:1013–17
    [Google Scholar]
  183. Werdich XQ, McCollum GW, Rajaratnam VS, Penn JS. 2004. Variable oxygen and retinal VEGF levels: correlation with incidence and severity of pathology in a rat model of oxygen-induced retinopathy. Exp. Eye Res. 79:623–30
    [Google Scholar]
  184. Wilkinson-Berka JL, Rana I, Armani R, Agrotis A 2013. Reactive oxygen species, Nox and angiotensin II in angiogenesis: implications for retinopathy. Clin. Sci. 124:597–615
    [Google Scholar]
  185. Woolard J, Wang WY, Bevan HS, Qiu Y, Morbidelli L et al. 2004. VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 64:7822–35
    [Google Scholar]
  186. Wu WC, Lien R, Liao PJ, Wang NK, Chen YP et al. 2015. Serum levels of vascular endothelial growth factor and related factors after intravitreous bevacizumab injection for retinopathy of prematurity. JAMA Ophthalmol. 133:391–97
    [Google Scholar]
  187. Xin H, Biswas N, Li P, Zhong C, Chan TC et al. 2021. Heparin-binding VEGFR1 variants as long-acting VEGF inhibitors for treatment of intraocular neovascular disorders. PNAS 118:e1921252118
    [Google Scholar]
  188. Yang MB, Rao S, Copenhagen DR, Lang RA. 2013. Length of day during early gestation as a predictor of risk for severe retinopathy of prematurity. Ophthalmology 120:2706–13
    [Google Scholar]
  189. Ye X, Wang Y, Cahill H, Yu M, Badea TC et al. 2009. Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell 139:285–98
    [Google Scholar]
  190. Yetkin-Arik B, Vogels IMC, Nowak-Sliwinska P, Weiss A, Houtkooper RH et al. 2019. The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis. Sci. Rep. 9:12608
    [Google Scholar]
  191. York JR, Landers S, Kirby RS, Arbogast PG, Penn JS. 2004. Arterial oxygen fluctuation and retinopathy of prematurity in very-low-birth-weight infants. J. Perinatol. 24:82–87
    [Google Scholar]
  192. Young TL, Anthony DC, Pierce E, Foley E, Smith LEH. 1997. Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J. Am. Assoc. Pediatr. Ophthalmol. Strabismus 1:105–10
    [Google Scholar]
  193. Zayed MA, Uppal A, Hartnett ME. 2010. New-onset maternal gestational hypertension and risk of retinopathy of prematurity. Investig. Ophthalmol. Vis. Sci. 51:4983–88
    [Google Scholar]
  194. Zeng G, Taylor SM, McColm JR, Kappas NC, Kearney JB et al. 2007. Orientation of endothelial cell division is regulated by VEGF signaling during blood vessel formation. Blood 109:1345–52
    [Google Scholar]
  195. Zhou R, Zhang S, Gu X, Ge Y, Zhong D et al. 2018. Adenosine A2A receptor antagonists act at the hyperoxic phase to confer protection against retinopathy. Mol. Med. 24:41
    [Google Scholar]
  196. Zippel N, Kenny CH, Wu H, Garneau M, Kroe-Barrett R et al. 2022. Sema3A antibody BI-X prevents cell permeability and cytoskeletal collapse in HRMECs and increases tip cell density in mouse oxygen-induced retinopathy. Transl. Vis. Sci. Technol. 11:17
    [Google Scholar]
/content/journals/10.1146/annurev-vision-093022-021420
Loading
/content/journals/10.1146/annurev-vision-093022-021420
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error