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Benzodiazepine and kainate receptor binding sites in the RCS rat retina

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Abstract

Background

The effect of age and photoreceptor degeneration on the kainate subtype of glutamate receptors and on the benzodiazepine-sensitive γ-aminobutyric acid-A receptors (GABAA) in normal and RCS (Royal College of Surgeons) rats were investigated.

Methods

[3H]Kainate and [3H]flunitrazepam were used as radioligands for kainate and GABAA/benzodiazepine receptors, respectively, using the quantitative receptor autoradiography technique.

Results

In both normal and RCS rat retina we observed that [3Η]flunitrazepam and [3Η]kainate binding levels were several times higher in inner plexiform layer (IPL) than in outer plexiform layer (OPL) at all four ages studied (P17, P35, P60 and P180). Age-related changes in receptor binding were observed in normal rat retina: [3Η]flunitrazepam binding showed a significant decrease of 25% between P17 and P60 in IPL ,and [3Η]kainate binding showed significant decreases between P17 and P35 in both synaptic layers (71% in IPL and 63% in OPL). Degeneration-related changes in benzodiazepine and kainate receptor binding were observed in RCS rat retina. In IPL, [3Η]flunitrazepam and [3Η]kainate binding levels were higher than in normal retina at P35 (by 24% and 86%, respectively). In OPL, [3Η]flunitrazepam binding was higher in RCS than in normal retina on P35 (74%) and also on P60 (62%).

Conclusions

The results indicate that postnatal changes occur in kainate and benzodiazepine receptor binding sites in OPL and IPL of the rat retina up to 6 months of age. The data also suggest that the receptor binding changes observed in the RCS retina could be a consequence of the primary photoreceptor degeneration.

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References

  1. Altstein M, Dudai Y, Vogel Z (1981) Benzodiazepine receptors in chick retina: development and cellular localization. Brain Res 206:198–202

    CAS  PubMed  Google Scholar 

  2. Bahn S, Volk B, Wisden W (1994) Kainate receptor gene expression in the development. J Neurosci 14:5525–5546

    CAS  PubMed  Google Scholar 

  3. Barnstable CJ (1993) Glutamate and GABA in retinal circuitry. Curr Opin Neurobiol 3:520–525

    CAS  PubMed  Google Scholar 

  4. Bok D, Hall MO (1971) The role of pigment epithelium in the etiology of inherited retinal dystrophy in the rat. J Cell Biol 49:664–682

    CAS  PubMed  Google Scholar 

  5. Boos R, Schneider H, Wässle H (1993) Voltage- and transmitter-gated currents of all amacrine cells in a slice preparation of the rat retina. J Neurosci 13:2874–2888

    CAS  PubMed  Google Scholar 

  6. Brandstätter JH, Hack I (2001) Localization of glutamate receptors at a complex synapse. The mammalian photoreceptor synapse. Cell Tissue Res 303:1–14

    PubMed  Google Scholar 

  7. Brandstätter JH, Hartveit E, Sassoe-Pognetto M, Wässle H (1994) Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. Eur J Neurosci 6:1100–1112

    PubMed  Google Scholar 

  8. Brandstätter JH, Koulen P, Wässle H (1997) Selective synaptic distribution of kainate receptor subunits in the two plexiform layers of the rat retina. J Neurosci17:9298–9307

    Google Scholar 

  9. D'Cruz PM, Yasumura D, Weir J, Matthes MT, Abderrahim H, La Vail MM, Vollrath D (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9:645–651

    Article  CAS  PubMed  Google Scholar 

  10. Duvoisin R, Zhang C, Hamassaki-Britto D and Britto L (1995) Changes in expression of glutamate receptor subunits following photoreceptor degeneration in the rd mouse retina. Neurosci Lett 183:83–86

    Article  CAS  PubMed  Google Scholar 

  11. Eisenfeld AJ, LaVail MM, LaVail JH (1984) Assessment of possible transneural changes in the retina of rats with inherited retinal dystrophy:cell size, number, synapses, and axonal transport by retinal ganglion cells. J Comp Neurol 223:22–34

    CAS  PubMed  Google Scholar 

  12. Euler T, Schneider H, Wassle H (1996) Glutamate responses of bipolar cells in a slice preparation of the rat retina. J Neurosci 16:2934–2944

    CAS  PubMed  Google Scholar 

  13. Fletcher E (2000) Alterations in neurochemistry during retinal degeneration. Microsc Res Techn 50:89–102

    Article  CAS  Google Scholar 

  14. Fletcher EL, Kalloniatis M (1997) Neurochemical development of the degenerating rat retina. J Comp Neurol 388:1–22

    Article  CAS  PubMed  Google Scholar 

  15. Fletcher EL, Koulen P, Wässle H (1998) GABA-A and GABA-C receptors on mammalian rod bipolar cells. J Comp Neurol 396:351–365

    Article  CAS  PubMed  Google Scholar 

  16. Flores-Herr N, Protti DA, Wässle H (2001) Synaptic currents generating the inhibitory surround of ganglion cells in the mammalian retina. J Neurosci 21:4852–4863

    CAS  PubMed  Google Scholar 

  17. Gal A, Li Y, Thimpson DA, Weir J, Orth U, Jacobson SG, Apfelstedt-Sylla E, Vollrath D (2000) Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet 26:270–271

    Article  CAS  PubMed  Google Scholar 

  18. Garcia-Ladona FJ, Gombos G (1993) Regional distribution of transient [3H]kainic acid-binding sites in the central nervous system of the developing mouse: an autoradiographic study. Neurosci Lett 151:209–213

    CAS  PubMed  Google Scholar 

  19. Green DG, Kapousta-Bruneau NV (1999) A dissection of the electroretinogram from the isolated rat retina with microelectrodes and drugs. Visual Neurosci 19:727–741

    Article  Google Scholar 

  20. Greferath U, Grunert U, Muller F, Wassle H (1994) Localization of GABA-A receptors in the rabbit retina. Cell Tissue Res 276:295–307

    Article  CAS  PubMed  Google Scholar 

  21. Greferath U, Grunert U, Fritschy JM, Stephenson A, Mohler H, Wassle H (1995) GABA-A receptor subunits have differential distributions in the rat retina: in situ hybridization and immunohistochemistry. J Comp Neurol 353:553–571

    CAS  PubMed  Google Scholar 

  22. Hamassaki-Britto DE, Hermans-Borgmeyer I, Heinemann S, Hugjies TE (1993) Expression of glutamate receptor genes in the mammalian retina: the localization of GluR1 through GluR7 mRNAs. J Neurosci 13:1888–1898

    CAS  PubMed  Google Scholar 

  23. Hartveit E (1997) Functional organization of cone bipolar cells in the rat retina. J Neurophysiol 77:1716–1730

    CAS  PubMed  Google Scholar 

  24. Kaitz M, Auerbach E (1979) Retinal degeneration in RCS rats raised under ambient light levels. Vision Res 19:79–81

    CAS  PubMed  Google Scholar 

  25. Koulen P (1999) Postnatal development of GABA-A receptor β1, β2/3, γ2 immunoreactivity in the rat retina. J Neurosci Res 57:185–194

    Article  CAS  PubMed  Google Scholar 

  26. Koulen P, Sassoe-Pognetto M, Grunert U, Wassle H (1996) Selective clustering of GABA-A and glycine receptors in the mammalian retina. J Neurosci 16:2127–2140

    CAS  PubMed  Google Scholar 

  27. La Vail MM (2001) Legacy of the RCS rats: impact of a seminal study on retinal cell biology and retinal degenerative diseases. Prog Brain Res 131:617–627

    PubMed  Google Scholar 

  28. Lin Z-S, Yazulla S (1994) Heterogeneity of GABAA receptor in goldfish retina. J Comp Neurol 345:429–439.

    CAS  PubMed  Google Scholar 

  29. Mehta AK, Ticku MK (1999) An update on GABAA receptors. Brain Res Rev 29:196–217

    CAS  PubMed  Google Scholar 

  30. Miller LP, Johnson AE, Gelhard RE, Insel TR (1990) The ontogeny of excitatory amino acid receptors in the rat forbrain. II. Kainic acid receptors. Neuroscience 35:45–51

    CAS  PubMed  Google Scholar 

  31. Müller F, Greferath U, Wässle H, Wisden W, Seeburg P (1992) Glutamate receptor expression in the rat retina. Neurosci Lett 138:179–182

    CAS  PubMed  Google Scholar 

  32. Paul SM, Zatz M, Skolnick P (1980) Demonstration of brain-specific benzodiazepine receptors in rat retina. Brain Res 187:243–6

    CAS  PubMed  Google Scholar 

  33. Peng Y-W, Blackstone CD, Huganir RL, Yau K-W (1995) Distribution of glutamate receptor subtypes in the vertebrate retina. Neuroscience 66:483–497

    CAS  PubMed  Google Scholar 

  34. Perlman I (1978) Dark-adaptation in abnormal (RCS) rats studied electroretinographically. J Physiol 278:161–175

    CAS  PubMed  Google Scholar 

  35. Protti DA, Gerschenfeld HM, Llano I (1997) GABAergic and glycinergic IPSCs in ganglion cells of rat retinal slices. J Neurosci 17:6075–6085

    CAS  PubMed  Google Scholar 

  36. Robins J, Ikeda H (1989) Benzodiazepines and the mammalian retina. I. Autoradiographic localization of receptor sites and the lack of effect on the electroretinogram. Brain Res 479:313–322

    PubMed  Google Scholar 

  37. Sassoe-Pognetto M, Wässle H (1997) Synaptogenesis in the rat retina: subcellular localization of glycine receptors, GABAA receptors, and the anchoring protein gefyrin. J Comp Neurol 381:158–174

    Article  CAS  PubMed  Google Scholar 

  38. Sieghart W, Drexler G, Supavilai P, Karobath M (1982) Properties of benzodiazepine receptors in rat retina. Exp Eye Res 34:961–7

    CAS  PubMed  Google Scholar 

  39. Somohano F, Roberts PJ, Lopez-Colome AM (1988) Maturational changes in retinal excitatory amino acid receptors. Brain Res 470:59–67

    CAS  PubMed  Google Scholar 

  40. Thoreson WB, Witkovsky P (1999) Glutamate receptors and circuits in the vertebrate retina. Prog Ret Eye Res 18:765–810

    Article  CAS  Google Scholar 

  41. Tso M, Zhang C, Abler A, Chang C-J, Wong F, Chang G-Q, Lam T (1994) Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats. Invest Ophthalmol Vis Sci 35:2693–2699

    CAS  PubMed  Google Scholar 

  42. Villegas-Perez 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

    Article  CAS  PubMed  Google Scholar 

  43. Wong P (1994) Apoptosis, retinitis pigmentosa and degeneration. Biochem Cell Biol 72:489–498

    CAS  PubMed  Google Scholar 

  44. Wurgiger K, Lichtenberger T, Hanitzsch R (2001) On-bipolar cells and depolarising third-order neurons as the origin of the ERG-b-wave in the RCS rat. Vision Res 41:1091–1101

    Article  PubMed  Google Scholar 

  45. Yang CY, Lin ZS, Yazulla S (1992) Localization of GABAA receptor subtypes in the tiger salamander retina. Vis Neurosci 8:57–64

    CAS  PubMed  Google Scholar 

  46. Yazulla S, Stuholme KM, Pinto LH (1997) Differences in the retinal GABA system among control, spastic mutant and retinal degeneration mutant mice. Vision Res 37:3471–3482

    Article  CAS  PubMed  Google Scholar 

  47. Zabrin MA, Anholt RRH (1991) Benzodiazepine receptors in the eye. Invest Opthalmol Vis Sci 32:2579–2587

    Google Scholar 

  48. Zabrin MA, Wamsley JK, Palacios JM, Kuhar MJ (1986) Autoradiographic localization of high affinity GABA, benzodiazepine, dopaminergic, adrenergic and muscarinic cholinergic receptors in the rat, monkey and human retina. Brain Res 374:75–92

    PubMed  Google Scholar 

  49. Zhang C, Hammassaki-Britto DE, Britto LRG, Duvoisin RM (1996). Expression of glutamate receptor subunit genes during development of the mouse retina. Neuroreport 8:335–340

    CAS  PubMed  Google Scholar 

  50. Zuo P, Ogita K, Yoneda Y (1992) Presence of the binding of a variety of ligands related to ionotropic excitatory amino acid receptors in rat retina. Brain Res 576:168–172

    CAS  PubMed  Google Scholar 

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Acknowledgements

Supported by a grant to A.M. from the K. Karatheodori Programme (Research Committee, University of Patras).

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Correspondence to Kalliopi Stasi.

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Stasi, K., Naskar, R., Thanos, S. et al. Benzodiazepine and kainate receptor binding sites in the RCS rat retina. Graefe's Arch Clin Exp Ophthalmol 241, 154–160 (2003). https://doi.org/10.1007/s00417-002-0611-7

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  • DOI: https://doi.org/10.1007/s00417-002-0611-7

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