Research Overview

Lois Smith's research is directed at understanding the causes of retinopathy of prematurity and on developing methods to prevent it. Recent investigations in her laboratory have focused both on the factors that stimulate and on those that suppress the development of ROP.

One study demonstrated that retinopathy of prematurity may be due to the loss of the natural source of insulin-like growth factor 1--which is critical to blood vessel growth in the eye--from the amniotic fluid. The loss of IGF-1 is common among babies who have been delivered very prematurely.

Another has indicated that the induction of receptors for vascular endothelial growth factor beta 1(VEGFR-1) may prevent the oxygen-induced vessel loss that precipitates the ischemia of ROP. At the same time, she also determined that at a later stage, overproduction of VEGF can lead to the rampant vessel growth that is responsible for ROP.

In the next phase of this research, Smith and colleagues are exploring the use of growth factors to promote healthy early vessel growth and on the use of growth-factor inhibitors to block abnormal late growth.

About Lois Smith

Lois Smith received her MD from Boston University School of Medicine. She completed an internship at Beth Israel Deaconess Medical Center, a residency at Massachusetts Eye and Ear Infirmary, and a fellowship at Children's Hospital Boston.

Researcher Services

Researcher Areas

  • Retinopathy of prematurity

Research Departments

PUBLICATIONS

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  1. Nilsson AK, Löfqvist C, Najm S, Hellgren G, Sävman K, Andersson MX, Smith LEH, Hellström A. Influence of Human Milk and Parenteral Lipid Emulsions on Serum Fatty Acid Profiles in Extremely Preterm Infants. JPEN J Parenter Enteral Nutr. 2018 Apr 21. View abstract
  2. Sveinsdóttir K, Ley D, Hövel H, Fellman V, Hüppi PS, Smith LEH, Hellström A, Hansen Pupp I. Relation of Retinopathy of Prematurity to Brain Volumes at Term Equivalent Age and Developmental Outcome at 2 Years of Corrected Age in Very Preterm Infants. Neonatology. 2018 Apr 12; 114(1):46-52. View abstract
  3. Löfqvist CA, Najm S, Hellgren G, Engström E, Sävman K, Nilsson AK, Andersson MX, Hård AL, Smith LEH, Hellström A. Association of Retinopathy of Prematurity With Low Levels of Arachidonic Acid: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2018 Mar 01; 136(3):271-277. View abstract
  4. Fu Z, Wang Z, Liu CH, Gong Y, Cakir B, Liegl R, Sun Y, Meng SS, Burnim SB, Arellano I, Moran E, Duran R, Poblete A, Cho SS, Talukdar S, Akula JD, Hellström A, Smith LEH. Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice. Diabetes. 2018 May; 67(5):974-985. View abstract
  5. Nilsson AK, Löfqvist C, Najm S, Hellgren G, Sävman K, Andersson MX, Smith LEH, Hellström A. Long-chain polyunsaturated fatty acids decline rapidly in milk from mothers delivering extremely preterm indicating the need for supplementation. Acta Paediatr. 2018 Feb 14. View abstract
  6. Pearsall EA, Cheng R, Zhou K, Takahashi Y, Matlock HG, Vadvalkar SS, Shin Y, Fredrick TW, Gantner ML, Meng S, Fu Z, Gong Y, Kinter M, Humphries KM, Szweda LI, Smith LEH, Ma JX. PPARa is essential for retinal lipid metabolism and neuronal survival. BMC Biol. 2017 Nov 28; 15(1):113. View abstract
  7. Hellgren G, Löfqvist C, Hansen-Pupp I, Gram M, Smith LE, Ley D, Hellström A. Increased postnatal concentrations of pro-inflammatory cytokines are associated with reduced IGF-I levels and retinopathy of prematurity. Growth Horm IGF Res. 2018 Apr; 39:19-24. View abstract
  8. Lundgren P, Hård AL, Wilde Å, Löfqvist C, Smith LEH, Hellström A. Implementing higher oxygen saturation targets reduced the impact of poor weight gain as a predictor for retinopathy of prematurity. Acta Paediatr. 2018 May; 107(5):767-773. View abstract
  9. Chen J, Fu Y, Day DS, Sun Y, Wang S, Liang X, Gu F, Zhang F, Stevens SM, Zhou P, Li K, Zhang Y, Lin RZ, Smith LEH, Zhang J, Sun K, Melero-Martin JM, Han Z, Park PJ, Zhang B, Pu WT. VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis. Nat Commun. 2017 08 29; 8(1):383. View abstract
  10. Fu Z, Liegl R, Wang Z, Gong Y, Liu CH, Sun Y, Cakir B, Burnim SB, Meng SS, Löfqvist C, SanGiovanni JP, Hellström A, Smith LEH. Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice. Invest Ophthalmol Vis Sci. 2017 08 01; 58(10):3862-3870. View abstract
  11. Agyemang AA, Sveinsdóttir K, Vallius S, Sveinsdóttir S, Bruschettini M, Romantsik O, Hellström A, Smith LEH, Ohlsson L, Holmqvist B, Gram M, Ley D. Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage? Transl Stroke Res. 2017 Jun 10. View abstract
  12. Wallace DK, Kraker RT, Freedman SF, Crouch ER, Hutchinson AK, Bhatt AR, Rogers DL, Yang MB, Haider KM, VanderVeen DK, Siatkowski RM, Dean TW, Beck RW, Repka MX, Smith LE, Good WV, Hartnett ME, Kong L, Holmes JM. Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study. JAMA Ophthalmol. 2017 Jun 01; 135(6):654-656. View abstract
  13. Najm S, Löfqvist C, Hellgren G, Engström E, Lundgren P, Hård AL, Lapillonne A, Sävman K, Nilsson AK, Andersson MX, Smith LEH, Hellström A. Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial. Clin Nutr ESPEN. 2017 Aug; 20:17-23. View abstract
  14. Sun Y, Lin Z, Liu CH, Gong Y, Liegl R, Fredrick TW, Meng SS, Burnim SB, Wang Z, Akula JD, Pu WT, Chen J, Smith LEH. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J Exp Med. 2017 Jun 05; 214(6):1753-1767. View abstract
  15. Levin LA, Miller JW, Zack DJ, Friedlander M, Smith LEH. Special Commentary: Early Clinical Development of Cell Replacement Therapy: Considerations for the National Eye Institute Audacious Goals Initiative. Ophthalmology. 2017 Jul; 124(7):926-934. View abstract
  16. Sun Y, Liegl R, Gong Y, Bühler A, Cakir B, Meng SS, Burnim SB, Liu CH, Reuer T, Zhang P, Walz JM, Ludwig F, Lange C, Agostini H, Böhringer D, Schlunck G, Smith LEH, Stahl A. Sema3f Protects Against Subretinal Neovascularization In Vivo. EBioMedicine. 2017 Apr; 18:281-287. View abstract
  17. Fu Z, Gong Y, Liegl R, Wang Z, Liu CH, Meng SS, Burnim SB, Saba NJ, Fredrick TW, Morss PC, Hellstrom A, Talukdar S, Smith LE. FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice. Cell Rep. 2017 02 14; 18(7):1606-1613. View abstract
  18. Hellstrom A, Ley D, Hallberg B, Lofqvist C, Hansen-Pupp I, Ramenghi LA, Borg J, Smith LEH, Hard AL. IGF-1 as a Drug for Preterm Infants: A Step-Wise Clinical Development. Curr Pharm Des. 2017; 23(38):5964-5970. View abstract
  19. Gong Y, Shao Z, Fu Z, Edin ML, Sun Y, Liegl RG, Wang Z, Liu CH, Burnim SB, Meng SS, Lih FB, SanGiovanni JP, Zeldin DC, Hellström A, Smith LEH. Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis. EBioMedicine. 2016 Nov; 13:201-211. View abstract
  20. Hellström A, Ley D, Hansen-Pupp I, Hallberg B, Ramenghi LA, Löfqvist C, Smith LE, Hård AL. IGF-I in the clinics: Use in retinopathy of prematurity. Growth Horm IGF Res. 2016 Oct - Dec; 30-31:75-80. View abstract
  21. Liegl R, Löfqvist C, Hellström A, Smith LE. IGF-1 in retinopathy of prematurity, a CNS neurovascular disease. Early Hum Dev. 2016 11; 102:13-19. View abstract
  22. Lundgren P, Lundberg L, Hellgren G, Holmström G, Hård AL, Smith LE, Wallin A, Hallberg B, Hellström A. Aggressive Posterior Retinopathy of Prematurity Is Associated with Multiple Infectious Episodes and Thrombocytopenia. Neonatology. 2017; 111(1):79-85. View abstract
  23. Hellström A, Ley D, Hansen-Pupp I, Hallberg B, Ramenghi LA, Löfqvist C, Smith LE, Hård AL. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants. Am J Perinatol. 2016 09; 33(11):1067-71. View abstract
  24. Moran EP, Wang Z, Chen J, Sapieha P, Smith LE, Ma JX. Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol. 2016 Sep 01; 311(3):H738-49. View abstract
  25. Gong Y, Fu Z, Edin ML, Liu CH, Wang Z, Shao Z, Fredrick TW, Saba NJ, Morss PC, Burnim SB, Meng SS, Lih FB, Lee KS, Moran EP, SanGiovanni JP, Hellström A, Hammock BD, Zeldin DC, Smith LE. Cytochrome P450 Oxidase 2C Inhibition Adds to ?-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization. Arterioscler Thromb Vasc Biol. 2016 Sep; 36(9):1919-27. View abstract
  26. Joyal JS, Sun Y, Gantner ML, Shao Z, Evans LP, Saba N, Fredrick T, Burnim S, Kim JS, Patel G, Juan AM, Hurst CG, Hatton CJ, Cui Z, Pierce KA, Bherer P, Aguilar E, Powner MB, Vevis K, Boisvert M, Fu Z, Levy E, Fruttiger M, Packard A, Rezende FA, Maranda B, Sapieha P, Chen J, Friedlander M, Clish CB, Smith LE. Corrigendum: Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1. Nat Med. 2016 06 07; 22(6):692. View abstract
  27. Fu Z, Gong Y, Löfqvist C, Hellström A, Smith LE. Review: adiponectin in retinopathy. Biochim Biophys Acta. 2016 Aug; 1862(8):1392-400. View abstract
  28. Joyal JS, Sun Y, Gantner ML, Shao Z, Evans LP, Saba N, Fredrick T, Burnim S, Kim JS, Patel G, Juan AM, Hurst CG, Hatton CJ, Cui Z, Pierce KA, Bherer P, Aguilar E, Powner MB, Vevis K, Boisvert M, Fu Z, Levy E, Fruttiger M, Packard A, Rezende FA, Maranda B, Sapieha P, Chen J, Friedlander M, Clish CB, Smith LE. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1. Nat Med. 2016 Apr; 22(4):439-45. View abstract
  29. Hellström A, Ley D, Hansen-Pupp I, Hallberg B, Löfqvist C, van Marter L, van Weissenbruch M, Ramenghi LA, Beardsall K, Dunger D, Hård AL, Smith LE. Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development. Acta Paediatr. 2016 Jun; 105(6):576-86. View abstract
  30. Wang Y, Tadjuidje E, Pandey RN, Stefater JA, Smith LE, Lang RA, Hegde RS. The Eyes Absent Proteins in Developmental and Pathological Angiogenesis. Am J Pathol. 2016 Mar; 186(3):568-78. View abstract
  31. Sun Y, Ju M, Lin Z, Fredrick TW, Evans LP, Tian KT, Saba NJ, Morss PC, Pu WT, Chen J, Stahl A, Joyal JS, Smith LE. SOCS3 in retinal neurons and glial cells suppresses VEGF signaling to prevent pathological neovascular growth. Sci Signal. 2015 Sep 22; 8(395):ra94. View abstract
  32. Hellgren G, Löfqvist C, Hård AL, Hansen-Pupp I, Gram M, Ley D, Smith LE, Hellström A. Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity. Pediatr Res. 2016 Jan; 79(1-1):70-5. View abstract
  33. Gong Y, Li J, Sun Y, Fu Z, Liu CH, Evans L, Tian K, Saba N, Fredrick T, Morss P, Chen J, Smith LE. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice. PLoS One. 2015; 10(7):e0132643. View abstract
  34. Srinivasan S, Chitalia V, Meyer RD, Hartsough E, Mehta M, Harrold I, Anderson N, Feng H, Smith LE, Jiang Y, Costello CE, Rahimi N. Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis. 2015 Oct; 18(4):449-62. View abstract
  35. SanGiovanni JP, Chen J, Gupta AS, Smith LE, Sapieha P, Lee PH. Netrin-1 - DCC Signaling Systems and Age-Related Macular Degeneration. PLoS One. 2015; 10(5):e0125548. View abstract
  36. Hellgren G, Engström E, Smith LE, Löfqvist C, Hellström A. Effect of Preterm Birth on Postnatal Apolipoprotein and Adipocytokine Profiles. Neonatology. 2015; 108(1):16-22. View abstract
  37. Fu Z, Lofqvist CA, Shao Z, Sun Y, Joyal JS, Hurst CG, Cui RZ, Evans LP, Tian K, SanGiovanni JP, Chen J, Ley D, Hansen Pupp I, Hellstrom A, Smith LE. Dietary ?-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin. Am J Clin Nutr. 2015 Apr; 101(4):879-88. View abstract
  38. Lundgren P, Kistner A, Andersson EM, Hansen Pupp I, Holmström G, Ley D, Niklasson A, Smith LE, Wu C, Hellström A, Löfqvist C. Low birth weight is a risk factor for severe retinopathy of prematurity depending on gestational age. PLoS One. 2014; 9(10):e109460. View abstract
  39. Stahl A, Hellstrom A, Smith LE. Insulin-like growth factor-1 and anti-vascular endothelial growth factor in retinopathy of prematurity: has the time come? Neonatology. 2014; 106(3):254-60. View abstract
  40. Rezende FA, Lapalme E, Qian CX, Smith LE, SanGiovanni JP, Sapieha P. Omega-3 supplementation combined with anti-vascular endothelial growth factor lowers vitreal levels of vascular endothelial growth factor in wet age-related macular degeneration. Am J Ophthalmol. 2014 Nov; 158(5):1071-78. View abstract
  41. Lundgren P, Wilde Å, Löfqvist C, Smith LE, Hård AL, Hellström A. Weight at first detection of retinopathy of prematurity predicts disease severity. Br J Ophthalmol. 2014 Nov; 98(11):1565-9. View abstract
  42. Shao Z, Fu Z, Stahl A, Joyal JS, Hatton C, Juan A, Hurst C, Evans L, Cui Z, Pei D, Gong Y, Xu D, Tian K, Bogardus H, Edin ML, Lih F, Sapieha P, Chen J, Panigrahy D, Hellstrom A, Zeldin DC, Smith LE. Cytochrome P450 2C8 ?3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report. Arterioscler Thromb Vasc Biol. 2014 Mar; 34(3):581-6. View abstract
  43. Michan S, Juan AM, Hurst CG, Cui Z, Evans LP, Hatton CJ, Pei DT, Ju M, Sinclair DA, Smith LE, Chen J. Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy. PLoS One. 2014; 9(1):e85031. View abstract
  44. Lundgren P, Stoltz Sjöström E, Domellöf M, Källen K, Holmström G, Hård AL, Smith LE, Löfqvist C, Hellström A. WINROP identifies severe retinopathy of prematurity at an early stage in a nation-based cohort of extremely preterm infants. PLoS One. 2013; 8(9):e73256. View abstract
  45. Chen J, Michan S, Juan AM, Hurst CG, Hatton CJ, Pei DT, Joyal JS, Evans LP, Cui Z, Stahl A, Sapieha P, Sinclair DA, Smith LE. Neuronal sirtuin1 mediates retinal vascular regeneration in oxygen-induced ischemic retinopathy. Angiogenesis. 2013 Oct; 16(4):985-92. View abstract
  46. Shao Z, Friedlander M, Hurst CG, Cui Z, Pei DT, Evans LP, Juan AM, Tahiri H, Tahir H, Duhamel F, Chen J, Sapieha P, Chemtob S, Joyal JS, Smith LE. Choroid sprouting assay: an ex vivo model of microvascular angiogenesis. PLoS One. 2013; 8(7):e69552. View abstract
  47. Hellström A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet. 2013 Oct 26; 382(9902):1445-57. View abstract
  48. Smith LE, Hard AL, Hellström A. The biology of retinopathy of prematurity: how knowledge of pathogenesis guides treatment. Clin Perinatol. 2013 Jun; 40(2):201-14. View abstract
  49. Buehler A, Sitaras N, Favret S, Bucher F, Berger S, Pielen A, Joyal JS, Juan AM, Martin G, Schlunck G, Agostini HT, Klagsbrun M, Smith LE, Sapieha P, Stahl A. Semaphorin 3F forms an anti-angiogenic barrier in outer retina. FEBS Lett. 2013 Jun 05; 587(11):1650-5. View abstract
  50. Chen J, Smith LE. Altered cholesterol homeostasis in aged macrophages linked to neovascular macular degeneration. Cell Metab. 2013 Apr 02; 17(4):471-2. View abstract
  51. Hård AL, Smith LE, Hellström A. Nutrition, insulin-like growth factor-1 and retinopathy of prematurity. Semin Fetal Neonatal Med. 2013 Feb 18. View abstract
  52. SanGiovanni JP, Chen J, Sapieha P, Aderman CM, Stahl A, Clemons TE, Chew EY, Smith LE. DNA sequence variants in PPARGC1A, a gene encoding a coactivator of the ?-3 LCPUFA sensing PPAR-RXR transcription complex, are associated with NV AMD and AMD-associated loci in genes of complement and VEGF signaling pathways. PLoS One. 2013; 8(1):e53155. View abstract
  53. Chen J, Hellstrom A, Smith LE. Author response: Different efficacy of propranolol in mice with oxygen-induced retinopathy: could differential effects of propranolol be related to differences in mouse strains? Invest Ophthalmol Vis Sci. 2012 Nov 19; 53(12):7728-9. View abstract
  54. Ley D, Hansen-Pupp I, Niklasson A, Domellöf M, Friberg LE, Borg J, Löfqvist C, Hellgren G, Smith LE, Hård AL, Hellström A. Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety. Pediatr Res. 2013 Jan; 73(1):68-74. View abstract
  55. Wu C, Löfqvist C, Smith LE, VanderVeen DK, Hellström A. Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity. Arch Ophthalmol. 2012 Aug; 130(8):992-9. View abstract
  56. Mammoto T, Chen J, Jiang E, Jiang A, Smith LE, Ingber DE, Mammoto A. LRP5 regulates development of lung microvessels and alveoli through the angiopoietin-Tie2 pathway. PLoS One. 2012; 7(7):e41596. View abstract
  57. Stahl A, Joyal JS, Chen J, Sapieha P, Juan AM, Hatton CJ, Pei DT, Hurst CG, Seaward MR, Krah NM, Dennison RJ, Greene ER, Boscolo E, Panigrahy D, Smith LE. SOCS3 is an endogenous inhibitor of pathologic angiogenesis. Blood. 2012 Oct 04; 120(14):2925-9. View abstract
  58. Chen J, Joyal JS, Hatton CJ, Juan AM, Pei DT, Hurst CG, Xu D, Stahl A, Hellstrom A, Smith LE. Propranolol inhibition of ß-adrenergic receptor does not suppress pathologic neovascularization in oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2012 May 17; 53(6):2968-77. View abstract
  59. Chen J, Smith LE. Protective inflammasome activation in AMD. Nat Med. 2012 May 04; 18(5):658-60. View abstract
  60. Chen J, Stahl A, Krah NM, Seaward MR, Joyal JS, Juan AM, Hatton CJ, Aderman CM, Dennison RJ, Willett KL, Sapieha P, Smith LE. Retinal expression of Wnt-pathway mediated genes in low-density lipoprotein receptor-related protein 5 (Lrp5) knockout mice. PLoS One. 2012; 7(1):e30203. View abstract
  61. Chen J, Stahl A, Krah NM, Seaward MR, Dennison RJ, Sapieha P, Hua J, Hatton CJ, Juan AM, Aderman CM, Willett KL, Guerin KI, Mammoto A, Campbell M, Smith LE. Wnt signaling mediates pathological vascular growth in proliferative retinopathy. Circulation. 2011 Oct 25; 124(17):1871-81. View abstract
  62. Tang M, Chen B, Lin T, Li Z, Pardo C, Pampo C, Chen J, Lien CL, Wu L, Ai L, Wang H, Yao K, Oh SP, Seto E, Smith LE, Siemann DW, Kladde MP, Cepko CL, Lu J. Restraint of angiogenesis by zinc finger transcription factor CTCF-dependent chromatin insulation. Proc Natl Acad Sci U S A. 2011 Sep 13; 108(37):15231-6. View abstract
  63. Zaniolo K, Sapieha P, Shao Z, Stahl A, Zhu T, Tremblay S, Picard E, Madaan A, Blais M, Lachapelle P, Mancini J, Hardy P, Smith LE, Ong H, Chemtob S. Ghrelin modulates physiologic and pathologic retinal angiogenesis through GHSR-1a. Invest Ophthalmol Vis Sci. 2011 Jul 23; 52(8):5376-86. View abstract
  64. Wikstrand MH, Hård AL, Niklasson A, Smith L, Löfqvist C, Hellström A. Maternal and neonatal factors associated with poor early weight gain and later retinopathy of prematurity. Acta Paediatr. 2011 Dec; 100(12):1528-33. View abstract
  65. Hua J, Guerin KI, Chen J, Michán S, Stahl A, Krah NM, Seaward MR, Dennison RJ, Juan AM, Hatton CJ, Sapieha P, Sinclair DA, Smith LE. Resveratrol inhibits pathologic retinal neovascularization in Vldlr(-/-) mice. Invest Ophthalmol Vis Sci. 2011 Apr; 52(5):2809-16. View abstract
  66. Chen J, Stahl A, Hellstrom A, Smith LE. Current update on retinopathy of prematurity: screening and treatment. Curr Opin Pediatr. 2011 Apr; 23(2):173-8. View abstract
  67. Stahl A, Krohne TU, Sapieha P, Chen J, Hellstrom A, Chew E, Holz FG, Smith LE. Lipid metabolites in the pathogenesis and treatment of neovascular eye disease. Br J Ophthalmol. 2011 Nov; 95(11):1496-501. View abstract
  68. Joyal JS, Sitaras N, Binet F, Rivera JC, Stahl A, Zaniolo K, Shao Z, Polosa A, Zhu T, Hamel D, Djavari M, Kunik D, Honoré JC, Picard E, Zabeida A, Varma DR, Hickson G, Mancini J, Klagsbrun M, Costantino S, Beauséjour C, Lachapelle P, Smith LE, Chemtob S, Sapieha P. Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A. Blood. 2011 Jun 02; 117(22):6024-35. View abstract
  69. Sapieha P, Stahl A, Chen J, Seaward MR, Willett KL, Krah NM, Dennison RJ, Connor KM, Aderman CM, Liclican E, Carughi A, Perelman D, Kanaoka Y, Sangiovanni JP, Gronert K, Smith LE. 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of ?-3 polyunsaturated fatty acids. Sci Transl Med. 2011 Feb 09; 3(69):69ra12. View abstract
  70. Parmalee NL, Schubert C, Merriam JE, Allikmets K, Bird AC, Gillies MC, Peto T, Figueroa M, Friedlander M, Fruttiger M, Greenwood J, Moss SE, Smith LE, Toomes C, Inglehearn CF, Allikmets R. Analysis of candidate genes for macular telangiectasia type 2. Mol Vis. 2010 Dec 14; 16:2718-26. View abstract
  71. Stahl A, Chen J, Sapieha P, Seaward MR, Krah NM, Dennison RJ, Favazza T, Bucher F, Löfqvist C, Ong H, Hellström A, Chemtob S, Akula JD, Smith LE. Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy. Am J Pathol. 2010 Dec; 177(6):2715-23. View abstract
  72. Hård AL, Löfqvist C, Fortes Filho JB, Procianoy RS, Smith L, Hellström A. Predicting proliferative retinopathy in a Brazilian population of preterm infants with the screening algorithm WINROP. Arch Ophthalmol. 2010 Nov; 128(11):1432-6. View abstract
  73. Stahl A, Buchwald A, Martin G, Junker B, Chen J, Hansen LL, Agostini HT, Smith LE, Feltgen N. Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema. Retina. 2010 Oct; 30(9):1524-9. View abstract
  74. Hoang MV, Smith LE, Senger DR. Calpain inhibitors reduce retinal hypoxia in ischemic retinopathy by improving neovascular architecture and functional perfusion. Biochim Biophys Acta. 2011 Apr; 1812(4):549-57. View abstract
  75. Hoang MV, Smith LE, Senger DR. Moderate GSK-3ß inhibition improves neovascular architecture, reduces vascular leakage, and reduces retinal hypoxia in a model of ischemic retinopathy. Angiogenesis. 2010 Sep; 13(3):269-77. View abstract
  76. Stahl A, Smith LE. An eye for discovery. J Clin Invest. 2010 Sep; 120(9):3008-11. View abstract
  77. Michán S, Li Y, Chou MM, Parrella E, Ge H, Long JM, Allard JS, Lewis K, Miller M, Xu W, Mervis RF, Chen J, Guerin KI, Smith LE, McBurney MW, Sinclair DA, Baudry M, de Cabo R, Longo VD. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci. 2010 Jul 21; 30(29):9695-707. View abstract
  78. Stahl A, Sapieha P, Connor KM, Sangiovanni JP, Chen J, Aderman CM, Willett KL, Krah NM, Dennison RJ, Seaward MR, Guerin KI, Hua J, Smith LE. Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy. Circ Res. 2010 Aug 20; 107(4):495-500. View abstract
  79. Stahl A, Connor KM, Sapieha P, Chen J, Dennison RJ, Krah NM, Seaward MR, Willett KL, Aderman CM, Guerin KI, Hua J, Löfqvist C, Hellström A, Smith LE. The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci. 2010 Jun; 51(6):2813-26. View abstract
  80. Chen ML, Guo L, Smith LE, Dammann CE, Dammann O. High or low oxygen saturation and severe retinopathy of prematurity: a meta-analysis. Pediatrics. 2010 Jun; 125(6):e1483-92. View abstract
  81. Wu C, Vanderveen DK, Hellström A, Löfqvist C, Smith LE. Longitudinal postnatal weight measurements for the prediction of retinopathy of prematurity. Arch Ophthalmol. 2010 Apr; 128(4):443-7. View abstract
  82. Connor KM, Krah NM, Dennison RJ, Aderman CM, Chen J, Guerin KI, Sapieha P, Stahl A, Willett KL, Smith LE. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc. 2009; 4(11):1565-73. View abstract
  83. Löfqvist C, Niklasson A, Engström E, Friberg LE, Camacho-Hübner C, Ley D, Borg J, Smith LE, Hellström A. A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants. Pediatr Res. 2009 May; 65(5):574-9. View abstract
  84. Löfqvist C, Hansen-Pupp I, Andersson E, Holm K, Smith LE, Ley D, Hellström A. Validation of a new retinopathy of prematurity screening method monitoring longitudinal postnatal weight and insulinlike growth factor I. Arch Ophthalmol. 2009 May; 127(5):622-7. View abstract
  85. Hellström A, Hård AL, Engström E, Niklasson A, Andersson E, Smith L, Löfqvist C. Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening. Pediatrics. 2009 Apr; 123(4):e638-45. View abstract
  86. Heidary G, Vanderveen D, Smith LE. Retinopathy of prematurity: current concepts in molecular pathogenesis. Semin Ophthalmol. 2009 Mar-Apr; 24(2):77-81. View abstract
  87. Mantagos IS, Vanderveen DK, Smith LE. Emerging treatments for retinopathy of prematurity. Semin Ophthalmol. 2009 Mar-Apr; 24(2):82-6. View abstract
  88. Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LE, Ingber DE. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature. 2009 Feb 26; 457(7233):1103-8. View abstract
  89. Lofqvist C, Willett KL, Aspegren O, Smith AC, Aderman CM, Connor KM, Chen J, Hellstrom A, Smith LE. Quantification and localization of the IGF/insulin system expression in retinal blood vessels and neurons during oxygen-induced retinopathy in mice. Invest Ophthalmol Vis Sci. 2009 Apr; 50(4):1831-7. View abstract
  90. Chen J, Connor KM, Aderman CM, Willett KL, Aspegren OP, Smith LE. Suppression of retinal neovascularization by erythropoietin siRNA in a mouse model of proliferative retinopathy. Invest Ophthalmol Vis Sci. 2009 Mar; 50(3):1329-35. View abstract
  91. English SB, Shih SC, Ramoni MF, Smith LE, Butte AJ. Use of Bayesian networks to probabilistically model and improve the likelihood of validation of microarray findings by RT-PCR. J Biomed Inform. 2009 Apr; 42(2):287-95. View abstract
  92. Smith LE. Through the eyes of a child: understanding retinopathy through ROP the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2008 Dec; 49(12):5177-82. View abstract
  93. Chen J, Smith LE. A double-edged sword: erythropoietin eyed in retinopathy of prematurity. J AAPOS. 2008 Jun; 12(3):221-2. View abstract
  94. Chen J, Connor KM, Aderman CM, Smith LE. Erythropoietin deficiency decreases vascular stability in mice. J Clin Invest. 2008 Feb; 118(2):526-33. View abstract
  95. Chen J, Connor KM, Smith LE. Overstaying their welcome: defective CX3CR1 microglia eyed in macular degeneration. J Clin Invest. 2007 Oct; 117(10):2758-62. View abstract
  96. Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, Hellstrom A, Kang JX, Chew EY, Salem N, Serhan CN, Smith LEH. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007 Jul; 13(7):868-873. View abstract
  97. Lofqvist C, Chen J, Connor KM, Smith AC, Aderman CM, Liu N, Pintar JE, Ludwig T, Hellstrom A, Smith LE. IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth. Proc Natl Acad Sci U S A. 2007 Jun 19; 104(25):10589-94. View abstract
  98. Chen J, Smith LE. Retinopathy of prematurity. Angiogenesis. 2007; 10(2):133-40. View abstract
  99. Löfqvist C, Andersson E, Sigurdsson J, Engström E, Hård AL, Niklasson A, Smith LE, Hellström A. Longitudinal postnatal weight and insulin-like growth factor I measurements in the prediction of retinopathy of prematurity. Arch Ophthalmol. 2006 Dec; 124(12):1711-8. View abstract
  100. Löfqvist C, Engström E, Sigurdsson J, Hård AL, Niklasson A, Ewald U, Holmström G, Smith LE, Hellström A. Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit. Pediatrics. 2006 Jun; 117(6):1930-8. View abstract
  101. Lutty GA, Chan-Ling T, Phelps DL, Adamis AP, Berns KI, Chan CK, Cole CH, D'Amore PA, Das A, Deng WT, Dobson V, Flynn JT, Friedlander M, Fulton A, Good WV, Grant MB, Hansen R, Hauswirth WW, Hardy RJ, Hinton DR, Hughes S, McLeod DS, Palmer EA, Patz A, Penn JS, Raisler BJ, Repka MX, Saint-Geniez M, Shaw LC, Shima DT, Smith BT, Smith LE, Tahija SG, Tasman W, Trese MT. Proceedings of the Third International Symposium on Retinopathy of Prematurity: an update on ROP from the lab to the nursery (November 2003, Anaheim, California). Mol Vis. 2006 May 23; 12:532-80. View abstract
  102. Smith LE, Connor KM. A radically twisted lipid regulates vascular death. Nat Med. 2005 Dec; 11(12):1275-6. View abstract
  103. Shih SC, Smith LE. Quantitative multi-gene transcriptional profiling using real-time PCR with a master template. Exp Mol Pathol. 2005 Aug; 79(1):14-22. View abstract
  104. Notari L, Miller A, Martínez A, Amaral J, Ju M, Robinson G, Smith LE, Becerra SP. Pigment epithelium-derived factor is a substrate for matrix metalloproteinase type 2 and type 9: implications for downregulation in hypoxia. Invest Ophthalmol Vis Sci. 2005 Aug; 46(8):2736-47. View abstract
  105. Smith LE. IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate. 2005; 88(3):237-44. View abstract
  106. Greene AK, Burrows PE, Smith L, Mulliken JB. Periorbital lymphatic malformation: clinical course and management in 42 patients. Plast Reconstr Surg. 2005 Jan; 115(1):22-30. View abstract
  107. Adam RM, Eaton SH, Estrada C, Nimgaonkar A, Shih SC, Smith LE, Kohane IS, Bägli D, Freeman MR. Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells. Physiol Genomics. 2004 Dec 15; 20(1):36-44. View abstract
  108. Smith LE. Bone marrow-derived stem cells preserve cone vision in retinitis pigmentosa. J Clin Invest. 2004 Sep; 114(6):755-7. View abstract
  109. Smith LE. Can we restore aspects of the in utero environment in premature infants to prevent disease? Pediatrics. 2004 Aug; 114(2):491. View abstract
  110. Smith LE. Pathogenesis of retinopathy of prematurity. Growth Horm IGF Res. 2004 Jun; 14 Suppl A:S140-4. View abstract
  111. Shih SC, Ju M, Liu N, Mo JR, Ney JJ, Smith LE. Transforming growth factor beta1 induction of vascular endothelial growth factor receptor 1: mechanism of pericyte-induced vascular survival in vivo. Proc Natl Acad Sci U S A. 2003 Dec 23; 100(26):15859-64. View abstract
  112. Smith LE. Pathogenesis of retinopathy of prematurity. Semin Neonatol. 2003 Dec; 8(6):469-73. View abstract
  113. Dallabrida SM, Zurakowski D, Shih SC, Smith LE, Folkman J, Moulton KS, Rupnick MA. Adipose tissue growth and regression are regulated by angiopoietin-1. Biochem Biophys Res Commun. 2003 Nov 21; 311(3):563-71. View abstract
  114. Hellström A, Engström E, Hård AL, Albertsson-Wikland K, Carlsson B, Niklasson A, Löfqvist C, Svensson E, Holm S, Ewald U, Holmström G, Smith LE. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics. 2003 Nov; 112(5):1016-20. View abstract
  115. Shih SC, Ju M, Liu N, Smith LE. Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity. J Clin Invest. 2003 Jul; 112(1):50-7. View abstract
  116. Calvo A, Yokoyama Y, Smith LE, Ali I, Shih SC, Feldman AL, Libutti SK, Sundaram R, Green JE. Inhibition of the mammary carcinoma angiogenic switch in C3(1)/SV40 transgenic mice by a mutated form of human endostatin. Int J Cancer. 2002 Sep 20; 101(3):224-34. View abstract
  117. Smith LE. Stem cells go for the eyes. Nat Med. 2002 Sep; 8(9):932-4. View abstract
  118. Hellström A, Carlsson B, Niklasson A, Segnestam K, Boguszewski M, de Lacerda L, Savage M, Svensson E, Smith L, Weinberger D, Albertsson Wikland K, Laron Z. IGF-I is critical for normal vascularization of the human retina. J Clin Endocrinol Metab. 2002 Jul; 87(7):3413-6. View abstract
  119. Shih SC, Robinson GS, Perruzzi CA, Calvo A, Desai K, Green JE, Ali IU, Smith LE, Senger DR. Molecular profiling of angiogenesis markers. Am J Pathol. 2002 Jul; 161(1):35-41. View abstract
  120. Smith LE, Hellstrom A. RP-forme fruste. J Perinatol. 2002 Apr-May; 22(3):257; author reply 257-8. View abstract
  121. Smith LE. Pathogenesis of retinopathy of prematurity. Acta Paediatr Suppl. 2002; 91(437):26-8. View abstract
  122. Bernstein SL, Russell P, Wong P, Fishelevich R, Smith LE. Heat shock protein 90 in retinal ganglion cells: association with axonally transported proteins. Vis Neurosci. 2001 May-Jun; 18(3):429-36. View abstract
  123. Robinson GS, Ju M, Shih SC, Xu X, McMahon G, Caldwell RB, Smith LE. Nonvascular role for VEGF: VEGFR-1, 2 activity is critical for neural retinal development. FASEB J. 2001 May; 15(7):1215-7. View abstract
  124. Hellstrom A, Perruzzi C, Ju M, Engstrom E, Hard AL, Liu JL, Albertsson-Wikland K, Carlsson B, Niklasson A, Sjodell L, LeRoith D, Senger DR, Smith LE. Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. Proc Natl Acad Sci U S A. 2001 May 08; 98(10):5804-8. View abstract
  125. Ali IU, Senger DR, Smith LE. Angiogenesis as a potential biomarker in prostate cancer chemoprevention trials. Urology. 2001 Apr; 57(4 Suppl 1):143-7. View abstract
  126. Driver SE, Robinson GS, Flanagan J, Shen W, Smith LE, Thomas DW, Roberts PC. Oligonucleotide-based inhibition of embryonic gene expression. Nat Biotechnol. 1999 Dec; 17(12):1184-7. View abstract
  127. Smith LE, Shen W, Perruzzi C, Soker S, Kinose F, Xu X, Robinson G, Driver S, Bischoff J, Zhang B, Schaeffer JM, Senger DR. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med. 1999 Dec; 5(12):1390-5. View abstract
  128. Stephan DA, Gillanders E, Vanderveen D, Freas-Lutz D, Wistow G, Baxevanis AD, Robbins CM, VanAuken A, Quesenberry MI, Bailey-Wilson J, Jou SH, Trent JM, Smith L, Brownstein MJ. Progressive juvenile onset punctate cataracts caused by mutation of the gamma D crystalline gene. Proc Natl Acad Sci USA. 1999; 96(3):1008-1012. View abstract
  129. Aiello LP, Bursell SE, Clermont A, Duh E, Ishii H, Takagi C, Mori F, Ciulla TA, Ways K, Jirousek M, Smith LE, King GL. Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes. 1997 Sep; 46(9):1473-80. View abstract
  130. Smith LE, Kopchick JJ, Chen W, Knapp J, Kinose F, Daley D, Foley E, Smith RG, Schaeffer JM. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science. 1997 Jun 13; 276(5319):1706-9. View abstract
  131. Young TL, Anthony DC, Pierce E, Foley E, Smith LE. Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS. 1997 Jun; 1(2):105-10. View abstract
  132. Pierce EA, Foley ED, Smith LE. Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol. 1996 Oct; 114(10):1219-28. View abstract
  133. Robinson GS, Pierce EA, Rook SL, Foley E, Webb R, Smith LE. Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy. Proc Natl Acad Sci U S A. 1996 May 14; 93(10):4851-6. View abstract
  134. Aiello LP, Pierce EA, Foley ED, Takagi H, Chen H, Riddle L, Ferrara N, King GL, Smith LE. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A. 1995 Nov 07; 92(23):10457-61. View abstract
  135. Seow WK, Needleman HL, Smith LE, Holtzman D, Najjar S. Enamel hypoplasia, bilateral cataracts, and aqueductal stenosis: a new syndrome? Am J Med Genet. 1995 Sep 25; 58(4):371-3. View abstract
  136. Burns JC, Wright JD, Newburger JW, Schneeberger EE, Mierau GW, Smith LE. Conjunctival biopsy in patients with Kawasaki disease. Pediatr Pathol Lab Med. 1995 Jul-Aug; 15(4):547-53. View abstract
  137. Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LE. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A. 1995 Jan 31; 92(3):905-9. View abstract
  138. Wesolowski E, Smith LE. Effect of light on oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994 Jan; 35(1):112-9. View abstract
  139. Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, D'Amore PA. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994 Jan; 35(1):101-11. View abstract
  140. D'Amato R, Wesolowski E, Smith LE. Microscopic visualization of the retina by angiography with high-molecular-weight fluorescein-labeled dextrans in the mouse. Microvasc Res. 1993 Sep; 46(2):135-42. View abstract
  141. Smith LE, Sweet E, Freedman S, D'Amore PA. Alterations in endothelial superoxide dismutase levels as a function of growth state in vitro. Invest Ophthalmol Vis Sci. 1992 Jan; 33(1):36-41. View abstract
  142. Smith, LEH, Burns, J. Kawasaki Syndrome in the Eye. Pediatric Infectious Disease Journal. 1989; 8:116-118. View abstract
  143. Connolly SE, Hores TA, Smith LE, D'Amore PA. Characterization of vascular development in the mouse retina. Microvasc Res. 1988 Nov; 36(3):275-90. View abstract
  144. Hoover DL, Smith LE, Turner SJ, Gelber RD, Sallan SE. Ophthalmic evaluation of survivors of acute lymphoblastic leukemia. Ophthalmology. 1988 Feb; 95(2):151-5. View abstract
  145. Sadun, AA, Johnson, DM, Smith, LEH. Neuroanatomy of the human visual system: part II- Retinal projections to the superior colliculus and pulvinar. Neuro-ophthalmology. 1986; 6(6):362-370. View abstract
  146. Sadun AA, Schaechter JD, Smith LE. A retinohypothalamic pathway in man: light mediation of circadian rhythms. Brain Res. 1984 Jun 08; 302(2):371-7. View abstract
  147. Sadun AA, Smith LE, Kenyon KR. Paraphenylenediamine: a new method for tracing human visual pathways. J Neuropathol Exp Neurol. 1983 Mar; 42(2):200-6. View abstract
  148. Beatty, RM, Sadun, AA, Smith, LEH, Vonsateil, JP, Richardson, EP. Direct demonstration of transsynaptic degeneration in the human visual system. Journal of Neurology Neurosurgery Psychiatry. 1982; 45:143. View abstract
  149. Mohr LH, Smith LE, Raftery MA. Alpha-secondary tritium isotope effects in the aqueous hydrolysis of glycopyranosides of N-acetyl-beta-D-glucosamine. Arch Biochem Biophys. 1973 Nov; 159(1):505-11. View abstract
  150. Smith LE, Mohr LH, Raftery MA. Mechanism for lysozyme-catalyzed hydrolysis. J Am Chem Soc. 1973 Oct 31; 95(22):7497-7500. View abstract