Advertisement

International Ophthalmology

, Volume 34, Issue 4, pp 989–997 | Cite as

Diabetic retinopathy and pregnancy

  • Nicola Pescosolido
  • Orazio Campagna
  • Andrea Barbato
Review Paper

Abstract

Diabetes mellitus and pregnancy have reciprocal influences between them, therefore diabetes mellitus may complicate the course of pregnancy as well as pregnancy can worsen the performance of diabetes especially at the fundus oculi. Several factors seem to play a role in retinal neovascularization. Actually it’s not possible to understand the mechanisms underlying this progression. Moreover chronic hyperglycemia leads to several events such as: the activation of aldose reductase metabolic pathway, the activation of the diacylglycerol-protein kinase C, the non-enzymatic glycation of proteins with formation of advanced glycation endproducts and the increase of hexosamines pathway. Although every structure of the eye can be affected by diabetes, retinal tissue, with all its vessels, is particularly susceptible. Pregnancy may promote the onset of diabetic retinopathy, in about 10 % of cases, as well as contribute to its worsening when already present. The proliferative retinopathy must always be treated; treatment should be earlier in pregnant women compared to non-pregnant women. Pregnancy can also cause macular edema; it spontaneously regresses during the postpartum and therefore does not require immediate treatment. In summary, collaboration between the various specialists is primary to ensure the best outcomes for both mother’s health and sight, and fetus’ health.

Keywords

Diabetes mellitus Diabetic retinopathy Hyperglycemia Pregnancy Oxidative stress 

Notes

Acknowledgments

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Adamis AP, Aiello LP, D’Amato RA (1999) Angiogenesis and ophthalmic disease. Angiogenesis 3:9–14PubMedCrossRefGoogle Scholar
  2. 2.
    Bloomgarden ZT (2007) Screening for and managing diabetic retinopathy: current approaches. Am J Health Syst Pharm 64:S8–S14PubMedCrossRefGoogle Scholar
  3. 3.
    Campochiaro PA (2000) Retinal and choroidal neovascularization. J Cell Physiol 184:301–310PubMedCrossRefGoogle Scholar
  4. 4.
    Das A, McGuire PG (2003) Retinal and choroidal angiogenesis: pathophysiology and strategies for inhibition. Prog Retin Eye Res 22:721–748PubMedCrossRefGoogle Scholar
  5. 5.
    Dhanabal M, Sethuraman N (2006) Endogenous angiogenesis inhibitors as therapeutic agents: historical perspective and future direction. Recent Patents Anticancer Drug Discov 1:223–236CrossRefGoogle Scholar
  6. 6.
    Nebbioso M, Federici M, Rusciano D, Evangelista M, Pescosolido N. Oxidative stress in pre-retinopathic diabetic subjects and antioxidants (2012) Diabetes Technology & Therapeutics. 14(3):257–63. doi: 10.1089/dia.2011.0172
  7. 7.
    Nebbioso M, Pranno F, Pescosolido N (2013) Lipoic acid in animal models and clinical use in diabetic retinopathy. Expert Opin Pharmacother 14(13):1829–1838PubMedCrossRefGoogle Scholar
  8. 8.
    Dorrell M, Uusitalo-Jarvinen H, Aguilar E, Friedlander M (2007) Ocular neovascularization: basic mechanisms and therapeutic advances. Surv Ophthalmol 52(S 1):S3-S19Google Scholar
  9. 9.
    Nebbioso M, Scarsella G, Tafani M, Pescosolido N (2013) Mechanisms of ocular neuroprotection by antioxidant molecole in animal models. J Biol Regul Homeost Agents 27(1):197–209PubMedGoogle Scholar
  10. 10.
    Pescosolido N, Giannotti R, Plateroti AM, Pascarella A, Nebbioso M (2013) Curcumin: therapeutical Potential in Ophthalmology. Planta Med 79(1–6). doi: 10.1055/s-0033-1351074
  11. 11.
    Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6(4):389–395PubMedCrossRefGoogle Scholar
  12. 12.
    Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3(6):401–410PubMedCrossRefGoogle Scholar
  13. 13.
    Bruick RK., McKnight SL (2001) A conserved family of prolyl-4-hydroxylases that modify HIF. Science;294(5545):1337–1340Google Scholar
  14. 14.
    Nyberg P, Xie L, Kalluri R (2005) Endogenous inhibitors of angiogenesis. Cancer Res 65:3967–3979PubMedCrossRefGoogle Scholar
  15. 15.
    Simó R, Carrasco E, García-Ramirez M, Hernández C (2006) Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev 2:71–98PubMedCrossRefGoogle Scholar
  16. 16.
    Stone J, Maslim J (1997) Mechanisms of retinal angiogenesis. Prog Retin Eye Res 16:157–181CrossRefGoogle Scholar
  17. 17.
    Zhang SX, Ma JX (2007) Ocular neovascularization: implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res 26:1–37PubMedCrossRefGoogle Scholar
  18. 18.
    Aranda J, Rivera JC, Jeziorski MC, Riesgo-Escovar J, Nava G, Lopez-Barrera F, Quiroz-Mercado H, Berger P, Martinez de la Escalera G, Clapp C (2005) Prolactins are natural inhibitors of angiogenesis in the retina. Invest Ophthalmol Vis Sci 46:2947–2953PubMedCrossRefGoogle Scholar
  19. 19.
    Boujon CE, Bestetti GE, Abramo F, Locatelli V, Rossi GL (1995) The reduction of circulating growth hormone and prolactin in streptozocin-induced diabetic male rats is possibly caused by hypothalamic rather than pituitary changes. J Endocrinol 145:19–26PubMedCrossRefGoogle Scholar
  20. 20.
    Clapp C, Martial JA, Guzman RC, Rentier-Delure F, Weiner RI (1993) The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology 133:1292–1299PubMedGoogle Scholar
  21. 21.
    Steigerwalt R, Nebbioso M, Appendino G, Belcaro G, Ciammaichella G, Cornelli U, Luzzi R, Togni S, Dugall M, Cesarone MR, Ippolito E, Errichi BM, Ledda A, Hosoi 17 M, Corsi M (2012) Meriva®, a lecithinized curcumin delivery system, in diabetic microangiopathy and retinopathy. Panminerva Med 54(1S4):11–16Google Scholar
  22. 22.
    Corbacho AM, Martínez De La Escalera G, Clapp C (2002) Roles of prolactin and related members of the prolactin/growth hormone/placental lactogen family in angiogenesis. J Endocrinol 173:219–238PubMedCrossRefGoogle Scholar
  23. 23.
    D’Angelo G, Martini JF, Iiri T, Fantl WJ, Martial J, Weiner R (1999) 16 K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells. Mol Endocrinol 13:692–704PubMedCrossRefGoogle Scholar
  24. 24.
    Nguyen NQ, Tabruyn SP, Lins L, Lion M, Cornet AM, Lair F, Rentier-Delrue F, Brasseur R, Martial JA, Struman I (2006) Prolactin/growth hormone-derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis. Proc Natl Acad Sci USA 103:14319–14324PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Ando A, Yang A, Mori K, Yamada H, Yamada E, Takahashi K, Saikia J, Kim M, Melia M, Fishman M, Huang P, Campochiaro PA (2002) Nitric oxide is proangiogenic in the retina and choroid. J Cell Physiol 191:116–124PubMedCrossRefGoogle Scholar
  26. 26.
    Bouck N (2002) PEDF: anti-angiogenic guardian of ocular function. Trends Mol Med 8:330–334PubMedCrossRefGoogle Scholar
  27. 27.
    Caldwell RB, Bartoli M, Behzadian MA, El-Remessy AE, Al-Shabrawey M, Platt DH, Liou GI, Caldwell RW (2005) Vascular endothelial growth factor and diabetic retinopathy: role of oxidative stress. Curr Drug Targets 6:511–524PubMedCrossRefGoogle Scholar
  28. 28.
    Cerasola GA, Donatelli M, Sinagra D, Russo V, Amico LM, Lodato G (1981) Study of pituitary secretion in relation to retinopathy in patients with juvenile diabetes mellitus. Acta Diabetol Lat 18(319–328):18Google Scholar
  29. 29.
    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. Invest Ophthalmol Vis Sci 36:1201–1214PubMedGoogle Scholar
  30. 30.
    Clapp C, Aranda J, Gonzalez C, Jeziorski MC, Martinez de la Escalera G (2006) Vasoinhibins: endogenous regulators of angiogenesis and vascular function. Trends Endocrinol Metab 17:301–307PubMedCrossRefGoogle Scholar
  31. 31.
    Jain IS, Luthra CL, Das T (1967) Diabetic retinopathy and its relation to errors of refraction. Arch Ophthalmol 77(1):59–60PubMedCrossRefGoogle Scholar
  32. 32.
    Jain IS, Luthra CL (1967) Diabetic retinopathy. Its relationship with intraocular pressure. Arch Ophthalmol 78(2):198–200PubMedCrossRefGoogle Scholar
  33. 33.
    Omoti AE, Waziri-Erameh JM, Okeigbemen VW (2008) A review of the changes in the ophthalmic and visual system in pregnancy. Afr J Reprod Health 12(3):185–196PubMedGoogle Scholar
  34. 34.
    Garg P, Aggarwal P, Nepal J (2012) Ocular changes in pregnancy. Ophthalmol 4(7):150–161Google Scholar
  35. 35.
    Sheth BP (2008) Does pregnancy accelerate the rate of progression of diabetic retinopathy?: an update. Curr Diab Rep 8(4):270–273PubMedCrossRefGoogle Scholar
  36. 36.
    Klein BE, Moss SE, Klein R (1990) Effect of pregnancy on progression of diabetic retinopathy. Diabetes Care 13(1):34–40PubMedCrossRefGoogle Scholar
  37. 37.
    Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D (1996) Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 114(9):1079–1084Google Scholar
  38. 38.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 102(4):520-526. 19Google Scholar
  39. 39.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 102(4):527–532PubMedCrossRefGoogle Scholar
  40. 40.
    Chew EY, Klein ML, Ferris FL 3rd, Remaley NA, Murphy RP, Chantry K, Hoogwerf BJ, Miller D (1996) Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 114(9):1079–1084Google Scholar
  41. 41.
    Larinkari J, Laatikainen L, Ranta T, Mörönen P, Pesonen K, Laatikainen T (1982) Metabolic control and serum hormone levels in relation to retinopathy in diabetic pregnancy. Diabetologia 22(5):327–332PubMedCrossRefGoogle Scholar
  42. 42.
    Loukovaara S, Immonen I, Koistinen R, Rudge J, Teramo KA, Laatikainen L, Hiilesmaa V, Kaaja RJ (2004) Angiopoietic factors and retinopathy in pregnancies complicated with Type 1 diabetes. Diabet Med 21(7):697–704PubMedCrossRefGoogle Scholar
  43. 43.
    Loukovaara S, Immonen IJ, Yandle TG, Nicholls G, Hiilesmaa VK, Kaaja RJ (2005) Vasoactive mediators and retinopathy during type 1 diabetic pregnancy. Acta Ophthalmol Scand 83(1):57–62PubMedCrossRefGoogle Scholar
  44. 44.
    Loukovaara S, Immonen I, Koistinen R, Hiilesmaa V, Kaaja R (2005) Inflammatory markers and retinopathy in pregnancies complicated with type I diabetes Eye 19(4):422–430Google Scholar
  45. 45.
    Loukovaara S, Kaaja R, Immonen I (2002) Macular capillary blood flow velocity by blue-field entoptoscopy in diabetic and healthy women during pregnancy and the postpartum period. Graefes Arch Clin Exp Ophthalmol 240(12):977–982PubMedCrossRefGoogle Scholar
  46. 46.
    Senti J, Thiele DK, Anderson CM (2012) Maternal vitamin D status as a critical determinant in gestational diabetes. J Obstet Gynecol Neonatal Nurs 41(3):328–338PubMedCrossRefGoogle Scholar
  47. 47.
    Alzaim M, Wood RJ (2013) Vitamin D and gestational diabetes mellitus. Nutr Rev 71(3):158–167. 20Google Scholar
  48. 48.
    Shen J, Yang X, Xiao WH, Hackett SF, Sato Y, Campochiaro PA (2006) Vasohibin is up-regulated by VEGF in the retina and suppresses VEGF receptor 2 and retinal neovascularization. FASEB J 20(6):723–725PubMedGoogle Scholar
  49. 49.
    Triebel J, Macotela Y, de la Escalera GM, Clapp C (2011) Prolactin and vasoinhibins: endogenous players in diabetic retinopathy. IUBMB Life 63(10):806–810PubMedCrossRefGoogle Scholar
  50. 50.
    Clapp C, Thebault S, Jeziorski MC, Martínez De La Escalera G (2009) Peptide hormone regulation of angiogenesis. Physiol Rev 89(4):1177–1215PubMedCrossRefGoogle Scholar
  51. 51.
    Wakusawa R, Abe T, Sato H, Sonoda H, Sato M, Mitsuda Y, Takakura T, Fukushima T, Onami H, Nagai N, Ishikawa Y, Nishida K, Sato Y (2011) Suppression of choroidal neovascularization by vasohibin-1, a vascular endothelium-derived angiogenic inhibitor. Invest Ophthalmol Vis Sci;52(6):3272–80Google Scholar
  52. 52.
    Helen CC, Tajunisah I, Reddy SC (2011) Adverse outcomes in Type I diabetic pregnant women with proliferative diabetic retinopathy. J Ophthalmol 4(4):443–446Google Scholar
  53. 53.
    Spoerri PE, Caballero S, Wilson SH, Shaw LC, Grant MB (2003) Expression of IGFBP-3 by human retinal endothelial cell cultures: iGFBP-3 involvement in growth inhibition and apoptosis. Invest Ophthalmol Vis Sci 44(1):365–369PubMedCrossRefGoogle Scholar
  54. 54.
    Franklin SL, Ferry RJ, Cohen P (2003) Rapid insulin-like growth factor (IGF)-independent effects of IGF binding protein-3 on endothelial cell survival. J Clin Endocrinol Metab 88:900–907PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Loukovaaraa S, Immonena IJR, Koistinenb R, Rutanenb EM, Hiilesmaab V, Loukovaarab M, Kaaja RJ (2005) The insulin-like growth factor system and Type 1 diabetic retinopathy during pregnancy. J Diabetes and Its Complications 19:297–304CrossRefGoogle Scholar
  56. 56.
    Soubrane G, Canivet J, Coscas G (1985) Influence of pregnancy on the evolution of background retinopathy. Int Ophthalmol 8(249–255):21Google Scholar
  57. 57.
    Rahman W, Rahman FZ, Yassin S, Al-Suleiman SA, Rahman J (2007) Progression of retinopathy during pregnancy in type 1 diabetes mellitus. Clin Experiment Ophthalmol 35(3):231–236PubMedCrossRefGoogle Scholar
  58. 58.
    Gaucher D, Saleh M, Sauer A, Averous L, Bourcier T, Speeg-Schatz C (2010) Progression of diabetic retinopathy during pregnancy. J Fr Ophtalmol 33(5):355–361PubMedCrossRefGoogle Scholar
  59. 59.
    Emerson MV, Lauer AK (2007) Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema. BioDrugs 21:245–257PubMedCrossRefGoogle Scholar
  60. 60.
    Sheth BP (2002) Does pregnancy accelerate the rate of progression of diabetic retinopathy? Curr Diab Rep 2(4):327–330PubMedCrossRefGoogle Scholar
  61. 61.
    Dibble CM, Kochenour NK, Worley RJ, Tyler FH, Swartz M (1982) Effect of pregnancy on diabetic retinopathy. Obstet Gynecol 59(6):699–704PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Nicola Pescosolido
    • 1
  • Orazio Campagna
    • 2
  • Andrea Barbato
    • 2
  1. 1.Department of Cardiovascular, Respiratory, Nephrology, Geriatric and Anesthesiology Science“Sapienza” University of RomeRomeItaly
  2. 2.Department of Sense Organs, Centre of Ocular Electrophysiology“Sapienza” University of RomeRomeItaly

Personalised recommendations