Skip to main content

Advertisement

Log in

Effects of direct intravitreal dopamine injections on the development of lid-suture induced myopia in rabbits

  • Laboratory Investigation
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

Dopamine (DA) storage and release are reduced in form deprivation myopia (FDM) in a wide range of species, from chicks to primates. FDM can be prevented by treatment with DA agonists such as apomorphine, and paradoxically by the dopamine neurotoxin 6-hydroxydopamine. In this study, we increased the DA levels by direct intravitreal DA injections to learn if FDM can be suppressed in a rabbit model.

Methods

Seven-day-old rabbits were deprived of pattern vision by the suturing the right eyelids after natural eye opening. In the first group (FD, n=20), the right eye received form deprivation (FD) alone. In the second group (DA-FD, n=16), the deprived eye of 7-day-old rabbits received four intravitreal injections of 20 μg dopamine every 5 days. In the third group (saline-FD, n=16), the deprived eye received saline injections with the same schedule. The contralateral eye remained untreated as a control. At the end of the 8-week deprivation period, the effects of DA on refractive error, corneal curvature and ocular dimensions were assessed by streak retinoscopy, keratometry and A-scan ultrasonography, respectively.

Results

Eight weeks of FDM induced a myopic shift of −2.70±0.87 D (n=20) in treated eyes compared with contralateral eyes. The major structural correlate of the myopia appeared to be elongation of the vitreous chamber (0.7±0.3 mm, n=20) and axial elongation (0.9±0.3 mm, n=20), respectively. Repeated intravitreal injections of DA fully prevented the myopic shift (−0.06±0.37 D), elongation of the vitreous chamber (0.1±0.3 mm, n=16) and axial elongation (0.3±0.2 mm, n=16) due to lid suture, whereas saline injections had slight effect.

Conclusions

FD by suturing eyelids is an effective technique to induce a significant myopic shift, vitreous chamber and axial elongation in rabbits as a model of myopia development. These changes associated with FD were retarded by intravitreal injections of DA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Beresford JA, Crewther SG, Kiely PM, Crewther DP (2001) Comparison of refractive state and circumferential morphology of retina, choroid, and sclera in chick models of experimentally induced ametropia. Optom Vis Sci 78:40–49

    Article  PubMed  CAS  Google Scholar 

  2. Bryant MR, Kampmeier J, Er H, Kasetsuwan N, Sanchez-DiMartino D, Shah SS, McDonnell PJ (1999) PRK-induced anisometropia in the rabbit as a model of myopia. Graefe’s Arch Clin Exp Ophthalmol 237:161–165

    Article  CAS  Google Scholar 

  3. Cottriall CL, Brew J, Vessey KA, McBrien NA (2001) Diisopropylfluoro-phosphate alters retinal neurotransmitter levels and reduces experimentally-induced myopia. Naunyn Schmiedeberg’s Arch Pharmacol 364:372–382

    Article  CAS  Google Scholar 

  4. Feldkaemper M, Diether S, Kleine G, Schaeffel F (1999) Interactions of spatial and luminance information in the retina of chickens during myopia development. Exp Eye Res 68:105–115

    Article  PubMed  CAS  Google Scholar 

  5. Funata M, Tokoro T (1990) Scleral change in experimentally myopic monkeys. Graefe’s Arch Clin Exp Ophthalmol 228:174–179

    Article  CAS  Google Scholar 

  6. Hendrickson P, Rosenblum W (1985) Accommodation demand and deprivation in kitten ocular development. Invest Ophthalmol Vis Sci 26:343–349

    PubMed  CAS  Google Scholar 

  7. Guo SS, Sivak JG, Callender MG, Diehl-Jones B (1995) Retinal dopamine and lens induced refractive errors in chicks. Curr Eye Res 14:385–383

    Article  PubMed  CAS  Google Scholar 

  8. Iuvone PM, Tigges M, Fernandes A, Tigges J (1989) Dopamine synthesis and metabolism in rhesus monkey retina: development, aging, and the effects of monocular visual deprivation. Vis Neurosci 2:465–471

    PubMed  CAS  Google Scholar 

  9. Iuvone PM, Tigges M, Stone RA, Lambert S, Laties AM (1991) Effects of apomorphine, a dopamine receptor agonist, on ocular refraction and axial elongation in a primate model of myopia. Invest Ophthalmol Vis Sci 32:1674–1677

    PubMed  CAS  Google Scholar 

  10. Marsh-Tootle WL, Norton TT (1989) Refractive and structural measures of lid-suture myopia in tree shrew. Invest Ophthalmol Vis Sci 30:2245–2257

    PubMed  CAS  Google Scholar 

  11. Maurice DM, Mushin AJ (1966) Production of myopia in rabbits by raised body temperature and increased intraocular pressure. Lancet 2:1160–1162

    Article  PubMed  CAS  Google Scholar 

  12. McBrien NA, Moghaddam HO, New R, Williams LR (1993) Experimental myopia in a diurnal mammal (Sciurus carolinensis) with no accommodative ability. J Physiol 469:427–441

    PubMed  CAS  Google Scholar 

  13. McBrien NA, Norton TT (1992) The development of experimental myopia and ocular component dimensions in monocularly lid-sutured tree shrews (Tupaia belangeri). Vision Res 32:843–852

    Article  PubMed  CAS  Google Scholar 

  14. Megaw PL, Morgan IG, Boelen MK (1997) Dopaminergic behaviour in chicken retina and the effect of form deprivation. Aust N Z J Ophthalmol 25:76–78

    Article  Google Scholar 

  15. Megaw P, Morgan I, Boelen M (2001) Vitreal dihydroxyphenylacetic acid (DOPAC) as an index of retinal dopamine release. J Neurochem 76:1636–1644

    Article  PubMed  CAS  Google Scholar 

  16. Mohan M, Rao VA, Dada VK (1977) Experimental myopia in the rabbit. Exp Eye Res 25:33–38

    Article  PubMed  CAS  Google Scholar 

  17. Nathan J, Crewther SG, Crewther DP, Kiely PM (1984) Effects of retinal image degradation on ocular growth in cats. Invest Ophthalmol Vis Sci 25:1300–1306

    PubMed  CAS  Google Scholar 

  18. Ni J, Smith EL 3rd (1989) Effects of chronic optical defocus on the kitten’s refractive status. Vision Res 29:929–938

    Article  PubMed  CAS  Google Scholar 

  19. Norton TT, McBrien NA (1992) Normal development of refractive state and ocular component dimensions in the tree shrew (Tupaia belangeri). Vision Res 32:833–842

    Article  PubMed  CAS  Google Scholar 

  20. Prince JH (1964) The rabbit in eye research. Thomas, Springfield, IlI

    Google Scholar 

  21. Rohrer B, Spira AW, Stell WK (1993) Apomorphine blocks form-deprivation myopia in chickens by a dopamine D2-receptor mechanism acting in retina or pigmented epithelium. Vis Neurosci 10:447–453

    Article  PubMed  CAS  Google Scholar 

  22. Rohrer B, Tao J, Stell WK (1997) Basic fibroblast growth factor, its high and-low-affinity receptors, and their relationship to form deprivation myopia in the chick. Neuroscience 79:775–787

    Article  PubMed  CAS  Google Scholar 

  23. Schaeffel F, Hagel G, Bartmann M, Kohler K, Zrenner E (1994) 6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia. Vision Res 34:143–149

    Article  PubMed  CAS  Google Scholar 

  24. Schaeffel F, Howland HC (1991) Properties of the feedback loops controlling eye growth and refractive state in the chicken. Vision Res 31:717–734

    Article  PubMed  CAS  Google Scholar 

  25. Schmid KL, Wildsoet CF (2004) Inhibitory effects of apomorphine and atropine and their combination on myopia in chicks. Optom Vis Sci 81:137–147

    Article  PubMed  Google Scholar 

  26. Seko Y, Tanaka Y, Tokoro T (1997) Apomorphine inhibits the growth-stim-ulating effect of retinal pigment epithelium on scleral cells in vitro. Cell Bio Chem Funct 15:191–196

    Article  CAS  Google Scholar 

  27. Siegwart JT Jr, Norton TT (2001) Steady state mRNA levels in tree shrew sclera with form deprivation myopia and during recovery. Invest Ophthalmol Vis Sci 42:1153–1159

    PubMed  Google Scholar 

  28. Smith EL 3rd, Harwerth RS, Crawford ML, von Noorden GK (1987) Observations on the effects of form deprivation on the refractive status of the monkey. Invest Ophthalmol Vis Sci 28:1236–1245

    PubMed  Google Scholar 

  29. Smith EL 3rd, Hung LF (2000) Form-deprivation myopia in monkeys is a graded phenomenon. Vision Res 40:371–381

    Article  PubMed  Google Scholar 

  30. Stone RA, Lin T, Iuvone PM, Laties AM (1990) Postnatal control of ocular growth: dopaminergic mechanisms. Ciba Found Symp 155:45–57; discussion 57–62

    PubMed  CAS  Google Scholar 

  31. Stone RA, Lin T, Laties AM, Iuvone PM (1989) Retinal dopamine and form-deprivation myopia. Proc Natl Acad Sci USA 86:704–706

    Article  PubMed  CAS  Google Scholar 

  32. Tokoro T (1970) Experimental myopia in rabbits. Invest Ophthalmol Vis Sci 9:926–934

    CAS  Google Scholar 

  33. Verolino M, Nastri G, Sellitti L, Costagliola C (1999) Axial length increase in lid-sutured rabbits. Surv Ophthalmol 44(Suppl 1):s103–s108

    Article  PubMed  Google Scholar 

  34. Wallman J (1993) Retinal control of eye growth and refraction in progress in retinal research. Pergamon Press, London, 12:133–153

  35. Wallman J, Winawer J (2004) Homeostasis of eye growth and the question of myopia. Neuron 43:447–468

    Article  PubMed  CAS  Google Scholar 

  36. Wildsoet C, Wallman J (1995) Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks. Vision Res 35:1175–1194

    Article  PubMed  CAS  Google Scholar 

  37. Wioland N, Rodolf G, Bonavexture N (1990) Electrooculographic and electroretinographic study in the chicken after dopamine and haloperidol. Doc Ophthalmol 75:175–180

    Article  PubMed  CAS  Google Scholar 

  38. Yinon U (1984) Myopia induction in animals following alteration of the visual input during development: a review. Curr Eye Res 3:677–690

    Article  PubMed  CAS  Google Scholar 

  39. Zhong XW, Ge J, Deng WG, Chen XL, Huang J (2004) Expression of pax-6 in rhesus monkey of optical defocus induced myopia and form deprivation myopia. Chin Med J (Engl) 117:722–726

    CAS  Google Scholar 

  40. Zhong XW, Ge J, Nie HH, Chen XL, Huang J, Liu L (2004) Effects of photorefractive keratectomy-induced defocus on emmetropization of infant rhesus monkeys. Invest Ophthalmol Vis Sci 45:3806–3811

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Jojo W. Du at SUNY State College of Optometry, for her through reading and constructive revision of the manuscript. Her invaluable comments and suggestions on this paper are gratefully acknowledged. This study was supported by the National Nature Science Foundation of China (30200306), the Science and Technology Foundation of Guang Dong Province of China (2003C32715) and the Science and Technology Foundation of Guang Zhou City of China (2002J1-C0381).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jian Ge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gao, Q., Liu, Q., Ma, P. et al. Effects of direct intravitreal dopamine injections on the development of lid-suture induced myopia in rabbits. Graefe's Arch Clin Exp Ophthalmo 244, 1329–1335 (2006). https://doi.org/10.1007/s00417-006-0254-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-006-0254-1

Keywords

Navigation