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.
Similar content being viewed by others
References
Altstein M, Dudai Y, Vogel Z (1981) Benzodiazepine receptors in chick retina: development and cellular localization. Brain Res 206:198–202
Bahn S, Volk B, Wisden W (1994) Kainate receptor gene expression in the development. J Neurosci 14:5525–5546
Barnstable CJ (1993) Glutamate and GABA in retinal circuitry. Curr Opin Neurobiol 3:520–525
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
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
Brandstätter JH, Hack I (2001) Localization of glutamate receptors at a complex synapse. The mammalian photoreceptor synapse. Cell Tissue Res 303:1–14
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
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
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
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
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
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
Fletcher E (2000) Alterations in neurochemistry during retinal degeneration. Microsc Res Techn 50:89–102
Fletcher EL, Kalloniatis M (1997) Neurochemical development of the degenerating rat retina. J Comp Neurol 388:1–22
Fletcher EL, Koulen P, Wässle H (1998) GABA-A and GABA-C receptors on mammalian rod bipolar cells. J Comp Neurol 396:351–365
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
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
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
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
Greferath U, Grunert U, Muller F, Wassle H (1994) Localization of GABA-A receptors in the rabbit retina. Cell Tissue Res 276:295–307
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
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
Hartveit E (1997) Functional organization of cone bipolar cells in the rat retina. J Neurophysiol 77:1716–1730
Kaitz M, Auerbach E (1979) Retinal degeneration in RCS rats raised under ambient light levels. Vision Res 19:79–81
Koulen P (1999) Postnatal development of GABA-A receptor β1, β2/3, γ2 immunoreactivity in the rat retina. J Neurosci Res 57:185–194
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
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
Lin Z-S, Yazulla S (1994) Heterogeneity of GABAA receptor in goldfish retina. J Comp Neurol 345:429–439.
Mehta AK, Ticku MK (1999) An update on GABAA receptors. Brain Res Rev 29:196–217
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
Müller F, Greferath U, Wässle H, Wisden W, Seeburg P (1992) Glutamate receptor expression in the rat retina. Neurosci Lett 138:179–182
Paul SM, Zatz M, Skolnick P (1980) Demonstration of brain-specific benzodiazepine receptors in rat retina. Brain Res 187:243–6
Peng Y-W, Blackstone CD, Huganir RL, Yau K-W (1995) Distribution of glutamate receptor subtypes in the vertebrate retina. Neuroscience 66:483–497
Perlman I (1978) Dark-adaptation in abnormal (RCS) rats studied electroretinographically. J Physiol 278:161–175
Protti DA, Gerschenfeld HM, Llano I (1997) GABAergic and glycinergic IPSCs in ganglion cells of rat retinal slices. J Neurosci 17:6075–6085
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
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
Sieghart W, Drexler G, Supavilai P, Karobath M (1982) Properties of benzodiazepine receptors in rat retina. Exp Eye Res 34:961–7
Somohano F, Roberts PJ, Lopez-Colome AM (1988) Maturational changes in retinal excitatory amino acid receptors. Brain Res 470:59–67
Thoreson WB, Witkovsky P (1999) Glutamate receptors and circuits in the vertebrate retina. Prog Ret Eye Res 18:765–810
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
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
Wong P (1994) Apoptosis, retinitis pigmentosa and degeneration. Biochem Cell Biol 72:489–498
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
Yang CY, Lin ZS, Yazulla S (1992) Localization of GABAA receptor subtypes in the tiger salamander retina. Vis Neurosci 8:57–64
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
Zabrin MA, Anholt RRH (1991) Benzodiazepine receptors in the eye. Invest Opthalmol Vis Sci 32:2579–2587
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
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
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
Acknowledgements
Supported by a grant to A.M. from the K. Karatheodori Programme (Research Committee, University of Patras).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-002-0611-7