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Induction of hyperglycaemia in zebrafish (Danio rerio) leads to morphological changes in the retina

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Abstract

Diabetes affects over 16 million Americans yearly, resulting in hyperglycaemia and microvascular complications, including retinopathy, neuropathy and nephropathy. Animal models have been developed to examine the immunological aspects of type 1 diabetes and the pathogenic mechanisms associated with diabetic retinopathy, but the methods of diabetes induction raise concerns regarding these models. Zebrafish (Danio rerio) have been used extensively to study developmental processes and mutant zebrafish strains have been used to examine vision disease present in humans. In this paper, we have induced hyperglycaemia in zebrafish by alternately immersing the fish in glucose solution or water. Eyes from untreated fish or fish exposed to alternating glucose/water solutions for 28 days were dissected, sectioned and stained to visualise cell bodies in the retina. In untreated fish retinas, the inner plexiform layer (IPL) and inner nuclear layer (INL) were approximately the same thickness, whereas in fish repeatedly exposed to glucose solutions the IPL was approximately 55% the thickness of the INL. Both the IPL and INL were significantly reduced in retinas of treated fish, compared to untreated fish, similar to that seen in other animal models of diabetes and in diabetic patients. These results suggest that zebrafish may be used as an animal model in which to study diabetic retinopathy.

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References

  1. -(2001) Diabetes, endocrinology, and metabolic diseases. National Center for Health Statistics www.cdc.gov/nchs/fastats/diabetes.htm

  2. Acha-Orea H, McDevitt HO (1987) The first external domain of the nonobese diabetic mouse class II I-A β chain is unique. Proc Natl Acad Sci USA 84:2435–2439

    Article  Google Scholar 

  3. Nakhooda AF, Like AA, Chapel CI, Wei CN, Marliss EB (1978) The spontaneous diabetic Wistar rat (the “BB” rat). Studies prior to and during development of the overt syndrome. Diabetologia 14:199–207

    Article  PubMed  CAS  Google Scholar 

  4. Yoshioka M, Kayo T, Ikeda T, Koizumi A (1997) A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57B1/6 (Akita) mutant mice. Diabetes 46:887–894

    Article  PubMed  CAS  Google Scholar 

  5. Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev 22:485–518

    PubMed  CAS  Google Scholar 

  6. Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48:2129–2139

    Article  PubMed  CAS  Google Scholar 

  7. Kazumi T, Yoshino G, Fujii S, Baba S (1978) Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Cancer Res 38:2144–2147

    PubMed  CAS  Google Scholar 

  8. IARC (1974) Monographs on the evaluation of the carcinogenic risk of chemicals to man. Some aromatic amines, hydrazine and related substances, N-nitroso compounds and miscellaneous alkylating agents. IARC, Lyon, France, p 286

    Google Scholar 

  9. Hampton T (2004) Scientists take aim at angiogenesis to treat degenerative eye diseases. JAMA 291:1309–1310

    Article  PubMed  CAS  Google Scholar 

  10. Lorenzi M, Gerhardinger C (2001) Early cellular and molecular changes induced by diabetes in the retina. Diabetologia 44:791–804

    Article  PubMed  CAS  Google Scholar 

  11. Sheetz M, King G (2002) Molecular understanding of hyperlycemia’s adverse effects for diabetic complications. JAMA 288:2579–2588

    Article  PubMed  CAS  Google Scholar 

  12. Li L, Dowling J (2000) Disruption of the olfactoretinal centrifugal pathway may relate to the visual system defect in night blindness b mutant zebrafish. J Neurosci 20:1883–1892

    PubMed  CAS  Google Scholar 

  13. Bilotta J, Saszik S (2002) Effects of embryonic exposure to ethanol on zebrafish visual function. Neurotoxicol Teratol 24:759–766

    Article  PubMed  CAS  Google Scholar 

  14. Bilotta J, Barnett JA, Hancock L, Saszik S (2004) Ethanol exposure alters zebrafish development: a novel model of fetal alcohol syndrome. Neurotoxicol Teratol 26:737–743

    Article  PubMed  CAS  Google Scholar 

  15. Chavin W, Young J (1970) Effects of alloxan upon goldfish (Carassius auratus L.). Gen Comp Endocrinol 14:436–460

    Article  Google Scholar 

  16. Barber AJ, Antonetti DA, Kern TS, Reiter CEN, Soans RS, Krady JK, Levison SW, Gardner TW, Bronson SK (2005) The Ins2Akita mouse as a model of early retinal complications in diabetes. Invest Ophthalomol Vis Sci 46:2210–2218

    Article  Google Scholar 

  17. Barber A (2003) A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Prog Neuropsychopharmacol Biol Psychiatry 27:283–290

    Article  PubMed  CAS  Google Scholar 

  18. Aizu Y, Oyanagi K, Hu J, Nakagawa H (2002) Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin-diabetic rats. Neuropathology 22:161–170

    Article  PubMed  Google Scholar 

  19. Martin PM, Roon P, van Ells TK, Ganapathy V, Smith SB (2004) Death of retinal neurons in streptozotocin-induced diabetic mice. Invest Ophthalmol Vis Sci 45:3330–3336

    Article  PubMed  Google Scholar 

  20. Wolter J (1961) Diabetic retinopathy. Am J Ophthalmol 51:1123–1141

    PubMed  CAS  Google Scholar 

  21. Bloodworth J (1962) Diabetic retinopathy. Diabetes 11:1–22

    PubMed  Google Scholar 

  22. Gerhard GS, Kauffman EJ, Wang X, Stewart R, Moore JL, Kasales CJ, Demidenki E, Cheng KC (2002) Life spans and senescent phenotypes in two strains of zebrafish (Danio rerio). Exp Gerontol 37:1055–1068

    Article  PubMed  Google Scholar 

  23. Bilotta J, Saszik S (2001) The zebrafish as a model visual system. Int J Dev Neurosci 19:621–629

    Article  PubMed  CAS  Google Scholar 

  24. Bilotta J (2000) Effects of abnormal lighting on the development of zebrafish visual behavior. Behav Brain Res 116:81–87

    Article  PubMed  CAS  Google Scholar 

  25. Brockerhoff SE, Hurley JB, Janssen-Bienhold U, Neuhauss SCF, Driever W, Dowling JE (1995) A behavioral screen for isolating zebrafish mutants with visual system defects. Proc Natl Acad Sci USA 92:10545–10549

    Article  PubMed  CAS  Google Scholar 

  26. Maaswinkel H, Riesbeck LE, Riley ME, Carr AL, Mulin JP, Nakamoto AT, Li L (2005) Behavioral screening for night-blindness mutants in zebrafish reveals three new loci that cause dominant photoreceptor cell degeneration. Mech Ageing Dev 126:1079–1089

    Article  PubMed  CAS  Google Scholar 

  27. Dodd A, Curtis P, Williams L, Love D (2000) Zebrafish: bridging the gap between development and disease. Hum Mol Genet 9:2443–2449

    Article  PubMed  CAS  Google Scholar 

  28. Moyle P, Cech J (2000) Fishes: an introduction to ichthyology. Prentice Hall, Upper Saddle River, USA

    Google Scholar 

  29. Svoboda KR, Vijayaraghavan S, Tanguay RL (2002) Nicotinic receptors mediate changes in spinal motoneuron development and axonal pathfinding in embryonic zebrafish exposed to nicotine. J Neurosci 22:10731–10741

    PubMed  CAS  Google Scholar 

  30. Moon TW (2001) Glucose intolerance in teleost fish: fact or fiction? Comp Biochem Physiol B 129:243–249

    Article  PubMed  CAS  Google Scholar 

  31. Mommsen TP, Plisetskaya EM (1991) Insulin in fishes and agnathans: history, structure and metabolic regulation. Rev Aquat Sci 4:225–259

    CAS  Google Scholar 

  32. Jensen PJ, Gitlin JD, Carayannopoulos MO (2006) GLUT1 deficiency links nutrient availability and apoptosis during embryonic development. J Biol Chem 12:13382–13387

    Article  CAS  Google Scholar 

  33. Maures T, Chan SJ, Xu B, Sun H, Ding J, Duan C (2002) Structural, biochemical, and expression analysis of two distinct insulin-like growth factor I receptors and their ligands in zebrafish. Endocrinology 143:1858–1871

    Article  PubMed  CAS  Google Scholar 

  34. Pozios KC, Ding J, Degger B, Upton Z, Duan C (2001) IGFs stimulate zebrafish cell proliferation by activating MAP kinase and PI3-kinase-signaling pathways. Am J Physiol Regul Integr Comp Physiol 280:1230–1239

    Google Scholar 

  35. Kelley KM (1993) Experimental diabetes mellitus in a teleost fish. I. Effect of complete isletectomy and subsequent hormonal treatment on metabolism in the goby, Gillichthys mirabilis. Endocrinology 132:2689–2695

    Article  PubMed  CAS  Google Scholar 

  36. Ince BW, Thorpe A (1975) The effects of diabetogenic and hypoglycemic agents in the northern pike, Esox lucius L. Gen Pharmacol 6:109–113

    CAS  Google Scholar 

  37. Sison M, Cawker J, Buske C, Gerlai R (2006) Fishing for genes influencing vertebrate behavior: Zebrafish making headway. Lab Animal 35:33–39

    Article  PubMed  Google Scholar 

  38. Shin J, Fishman M (2002) From zebrafish to human: modular medical models. Annu Rev Genomics Hum Genet 3:311–340

    Article  PubMed  CAS  Google Scholar 

  39. Langheinrich U (2003) Zebrafish: a new model on the pharmaceutical catwalk. Bioessays 25:904–912

    Article  PubMed  CAS  Google Scholar 

  40. Rubinstein A (2003) Zebrafish: from disease modeling to drug discovery. Curr Opin Drug Discov Dev 6:218–223

    CAS  Google Scholar 

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Correspondence to L. S. Arneson.

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Gleeson, M., Connaughton, V. & Arneson, L.S. Induction of hyperglycaemia in zebrafish (Danio rerio) leads to morphological changes in the retina. Acta Diabetol 44, 157–163 (2007). https://doi.org/10.1007/s00592-007-0257-3

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  • DOI: https://doi.org/10.1007/s00592-007-0257-3

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