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Axonal transport deficit in the optic nerve of rats with inherited retinitis pigmentosa and experimentally induced glaucoma

Graefe's Archive for Clinical and Experimental Ophthalmology volume 246, pages 1553–1558 (2008)Cite this article

Abstract

Background

Aim of this study was to investigate the retrograde axonal transport from optic nerve (ON) to retinal ganglion cell (RGC) in two animal models: in Royal College of Surgeons (RCS) rats, a rat model for retinal degeneration, and in a rat model for glaucoma induced by elevated intraocular pressure (IOP).

Methods

To carry out this study, dextran tetramethylrhodamine (DTMR- an hydrophilic neurotracer dye) was injected into the ON; 24 hrs later, the retina was removed and the number of labeled RGCs of the experimental rats was counted and compared.

Results

The results of these studies showed that the number of fluorescent-labeled RGCs in RCS rats and in rats with elevated IOP was reduced compared to the number of labeled RGCs of their respective controls.

Conclusion

Our findings suggest that RCS rats are characterized not only by loss of photoreceptor cells but also by functional deficits of RGCs.

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References

  1. Amendola T, Aloe L (2002) Developmental expression of nerve growth factor in the eye of rats affected by inherited retinopathy: correlative aspects with retinal structural degeneration. Arch Ital Biol 140:81–90

    PubMed  CAS  Google Scholar 

  2. Amendola T, Fiore M, Aloe L (2003) Postnatal changes in nerve growth factor and brain derived neurotrophic factor levels in the retina, visual cortex, and geniculate nucleus in rats with retinitis pigmentosa. Neurosci Lett 345:37–40, doi:10.1016/S0304-3940(03)00491-9

    PubMed  Article  CAS  Google Scholar 

  3. Bakalash S, Kessler A, Mizrahi T, Nussenblatt R, Schwartz M (2003) Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma. Invest Ophthalmol Vis Sci 44:3374–3381

    PubMed  Article  Google Scholar 

  4. Bakalash S, Rolls A, Lider O, Schwartz M (2007) Chondroitin sulfate-derived disaccharide protects retinal cells from elevated intraocular pressure in aged and immunocompromised rats. Invest Ophthalmol Vis Sci 48:1181–1190, doi:10.1167/iovs.05-1213

    PubMed  Article  Google Scholar 

  5. Chen ZS, Yin ZQ, Chen S, Wang SJ (2005) Electrophysiological changes of retinal ganglion cells in Royal College of Surgeons rats during retinal degeneration. Neuroreport 16:971–975, doi:10.1097/00001756-200506210-00018

    PubMed  Article  Google Scholar 

  6. Daiger SP, Bowne SJ, Sullivan LS (2007) Perspective on genes and mutations causing retinitis pigmentosa. Arch Ophthalmol 125(2):151–158, doi:10.1001/archopht.125.2.151

    PubMed  Article  CAS  Google Scholar 

  7. D'Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, LaVail MM et al (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9(4):645–651, doi:10.1093/hmg/9.4.645

    PubMed  Article  Google Scholar 

  8. Eitan S, Solomon A, Lavie V, Yoles E, Hirschberg DL, Belkin M et al (1994) Recovery of visual response of injured adult rat optic nerves treated with transglutaminase. Science 264:1764–1768, doi:10.1126/science.7911602

    PubMed  Article  CAS  Google Scholar 

  9. Fritzsch B (1993) Fast axonal diffusion of 3000 molecular weight dextran amines. J Neurosci Methods 50:95–103, doi:10.1016/0165-0270(93)90060-5

    PubMed  Article  CAS  Google Scholar 

  10. Gal A, Li Y, Thompson DA, Weir J, Orth U, Jacobson SG et al (2000) Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet 26:270–271, doi:10.1038/80002

    PubMed  Article  CAS  Google Scholar 

  11. Gartner S, Henkind P (1982) Pathology of retinitis pigmentosa. Ophthalmology 89:1425–1432

    PubMed  CAS  Google Scholar 

  12. Hanitzsch R, Zeumer C, Lichtenberger T, Wurziger K (1998) Impaired function of bipolar cell in the Royal College of Surgeons rat. Acta Anat (Basel) 162:119–126, doi:10.1159/000046476

    Article  CAS  Google Scholar 

  13. Hare W, WoldeMussie E, Lai R, Ton H, Ruiz G, Feldmann B et al (2001) Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey. Surv Ophthalmol 45(Suppl 3):S284–S289 discussion S295–296, doi:10.1016/S0039-6257(01)00200-4

    PubMed  Article  Google Scholar 

  14. Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368(9549):1795–1809

    PubMed  Article  CAS  Google Scholar 

  15. Lenzi L, Coassin M, Lambiase A, Bonini S, Amendola T, Aloe L (2005) Effect of exogenous administration of nerve growth factor in the retina of rats with inherited retinitis pigmentosa. Vision Res 45:1491–1500, doi:10.1016/j.visres.2004.12.020

    PubMed  Article  CAS  Google Scholar 

  16. Li ZY, Possin DE, Milam AH (1995) Histopathology of bone spicule pigmentation in retinitis pigmentosa. Ophthalmology 102:805–816,

    PubMed  CAS  Google Scholar 

  17. Milam AH, Li ZY, Fariss RN (1998) Histopathology of the human retina in retinitis pigmentosa. Prog Retin Eye Res 17:175–205, doi:10.1016/S1350-9462(97)00012-8

    PubMed  Article  CAS  Google Scholar 

  18. Minckler DS, Bunt AH, Johanson GW (1977) Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey. Invest Ophthalmol Vis Sci 16(5):426–441

    PubMed  CAS  Google Scholar 

  19. Otani A, Dorrell MI, Kinder K, Moreno SK, Nusinowitz S, Banin E et al (2004) Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest 114(6):756–774

    Google Scholar 

  20. Morrison JC, Johnson EC, Cepurna W, Jia L (2005) Understanding mechanisms of pressure-induced optic nerve damage. Prog Retin Eye Res 24:217–240, doi:10.1016/j.preteyeres.2004.08.003

    PubMed  Article  Google Scholar 

  21. Newman NM, Stevens RA, Heckenlively JR (1987) Nerve fibre layer loss in diseases of the outer retinal layer. Br J Ophthalmol 71:21–26, doi:10.1136/bjo.71.1.21

    PubMed  Article  CAS  Google Scholar 

  22. Solomon AS, Lavie V, Hauben U, Monsonego A, Yoles E, Schwartz M (1996) Complete transection of rat optic nerve while sparing the meninges and the vasculature: an experimental model for optic nerve neuropathy and trauma. J Neurosci Methods 70:21–25, doi:10.1016/S0165-0270(96)00098-2

    PubMed  Article  CAS  Google Scholar 

  23. Steinberg RH (1994) Survival factors in retinal degenerations. Curr Opin Neurobiol 4:515–524, doi:10.1016/0959-4388(94)90052-3

    PubMed  Article  CAS  Google Scholar 

  24. Stone JL, Barlow WE, Humayun MS, de Juan E Jr, Milam AH (1992) Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol 110:1634–1639

    PubMed  Article  CAS  Google Scholar 

  25. Villegas-Pérez MP, Lawrence JM, Vidal-Sanz M, Lavail MM, Lund RD (1998) Ganglion cell loss in RCS rat retina: a result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium. J Comp Neurol 392:58–77, doi:10.1002/(SICI)1096-9861(19980302)392:1<58::AID-CNE5>3.0.CO;2-O

    PubMed  Article  Google Scholar 

  26. Villegas-Pérez MP, Vidal-Sanz M, Lund RD (1996) Mechanism of retinal ganglion cell loss in inherited retinal dystrophy. Neuroreport 7:1995–1999, doi:10.1097/00001756-199608120-00028

    PubMed  Article  Google Scholar 

  27. Walia S, Fishman GA, Edward DP, Lindeman M (2007) Retinal nerve fiber layer defects in RP patients. Invest Ophthalmol Vis Sci 48:4748–4752, doi:10.1167/iovs.07-0404

    PubMed  Article  Google Scholar 

  28. Wang DY, Chan WM, Tam PO, Baum L, Lam DS, Chong KK et al (2005) Gene mutations in retinitis pigmentosa and their clinical implications. Clin Chim Acta 351:5–16, doi:10.1016/j.cccn.2004.08.004

    PubMed  Article  CAS  Google Scholar 

  29. WoldeMussie E, Ruiz G, Wijono M, Wheeler LA (2001) Neuroprotection of retinal ganglion cells by brimonidine in rats with laser-induced chronic ocular hypertension. Invest Ophthalmol Vis Sci 42:2849–2855

    PubMed  CAS  Google Scholar 

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Acknowledgement

This study was supported by CNR to L. Aloe and by Grant N° RF-FGB-2005-150198 from Ministero della Salute and Fondazione Cassa di Risparmio di Roma, Italy

Author information

Affiliations

  1. Section of Neurobiology, Institute of Neurobiology and Molecular Medicine, CNR, Via del Fosso di Fiorano, 64/65, I-00143, Rome, Italy

    Valentina Sposato, Federica Sornelli & Luigi Aloe

  2. Department of Ophthalmology, University of Rome “Campus Bio-Medico”, Rome, Italy

    Alfonso Iovieno

Authors
  1. Valentina Sposato
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  2. Alfonso Iovieno
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  3. Federica Sornelli
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  4. Luigi Aloe
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Corresponding author

Correspondence to Luigi Aloe.

Additional information

Valentina Sposato and Alfonso Iovieno contributed equally to this work.

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Sposato, V., Iovieno, A., Sornelli, F. et al. Axonal transport deficit in the optic nerve of rats with inherited retinitis pigmentosa and experimentally induced glaucoma. Graefes Arch Clin Exp Ophthalmol 246, 1553–1558 (2008). https://doi.org/10.1007/s00417-008-0903-7

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  • DOI: https://doi.org/10.1007/s00417-008-0903-7

Keywords

  • Retinitis pigmentosa
  • Retinal ganglion cell
  • Glaucoma
  • Axonal transport
  • Rhodamine