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Localization of alpha 2 receptors in ocular tissues

Published online by Cambridge University Press:  06 November 2007

ELIZABETH WOLDEMUSSIE ,
MERCY WIJONO  and
DAVID POW
ELIZABETH WOLDEMUSSIE
Affiliation:
Pfizer, Department of Ocular Biology, San Diego, California
MERCY WIJONO
Affiliation:
Allergan, Inc., Department of Biological Sciences, Irvine, California
DAVID POW
Affiliation:
School of Biomedical Sciences, University of Newcastle, NSW, Australia
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Abstract

Alpha 2 adrenergic agonists are used for controlling intraocular pressure (IOP) in the treatment of glaucoma. They have also been shown to be neuroprotective to retinal cells in a variety of injury models. Despite this significance, the localization of the three known alpha 2 adrenergic receptors has not been unequivocally established. The aim of this study was to determine the location of the three alpha 2 adrenergic receptors in ocular tissues using immunohistochemical techniques. New antibodies were generated and their specificity was determined using Western blotting and preadsorption. In the anterior segment of the eye alpha 2A immunoreactivity was located in the nonpigmented ciliary epithelium, corneal, and conjunctival epithelia. Alpha 2B staining was not apparent in these tissues. Alpha 2C immunostaining was present in the membrane of pigmented ciliary epithelium and corneal and conjunctival epithelial cells. In the rat retina, all three receptor subtypes were present but were differentially localized. Alpha 2A was present in the somata of ganglion cell layer and inner nuclear layer somas, alpha 2B was located in the dendrites and axons of most of the neurons as well as glia, while alpha 2C was present in the somata and inner segment of the photoreceptors. In human and monkey retinas, similar pattern of labeling for alpha 2A and 2B receptors were observed, while alpha 2B was additionally present in the membranes of many cell somata in addition to dendrites and axons. Alpha 2C labeling was much weaker but exhibited similar pattern to that observed in the rat. These data provide additional information on the location of the alpha 2 receptors in the anterior portion of the eye and present new information on their specific location in the retina. This offers insights into possible targets for adrenergic agonists in a therapeutic context.

Keywords

Alpha 2 adrenergic receptorsPolyclonal antibodiesRetinaCiliary bodyRatHumanMonkey
Type
Research Article
Information
Visual Neuroscience , Volume 24 , Issue 5 , September 2007 , pp. 745 - 756
Copyright
© 2007 Cambridge University Press

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References

REFERENCES

Ahmed, F.A., Hegazy, K., Chaudhary, P. & Sharma, S.C. (2001). Neuroprotective effect of alpha(2) agonist (brimonidine) on adult rat retinal ganglion cells after increased intraocular pressure. Brain Research 913, 133–139.Google Scholar
Berlie, J.R., Iversen, L.J., Blaxall, H.S., Cooley, M.E., Chacko, D.M. & Bylund, D.B. (1995). Alpha-2 adrenergic receptors in the bovine retina. Presence of only the alpha-2D subtype. Investigative Ophthalmology & Visual Science 36, 1885–1892.Google Scholar
Brubaker, R.F. (1991). Flow of aqueous humor in humans [The Friedenwald Lecture]. Investigative Ophthalmology & Visual Science 32, 3145–3166.Google Scholar
Burke, J.A. & Potter, D.E. (1986). Ocular effects of a relatively selective alpha 2 agonist (UK-14, 304-18) in cats, rabbits and monkeys. Current Eye Research 5, 665–676.Google Scholar
Bylund, D.B., Blaxall, H.S., Iversen, L.J., Caron, M.G., Lefkowitz, R.J. & Lomasney, J.W. (1992). Pharmacological characteristics of alpha 2-adrenergic receptors: Comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Molecular Pharmacology 42, 1–5.Google Scholar
Bylund, D.B. & Chacko, D.M. (1999). Characterization of alpha2 adrenergic receptor subtypes in human ocular tissue homogenates. Investigative Ophthalmology & Visual Science 40, 2299–2306.Google Scholar
Bylund, D.B., Iversen, L.J., Matulka, W.J. & Chacko, D.M. (1997). Characterization of alpha-2D adrenergic receptor subtypes in bovine ocular tissue homogenates. Journal of Pharmacology and Experimental Therapeutics 281, 1171–1177.Google Scholar
Chu, T.C. & Candia, O.A. (1988). Role of alpha 1- and alpha 2-adrenergic receptors in Cl- transport across frog corneal epithelium. American Journal of Physiology 255, C724–C730.Google Scholar
Donello, J.E., Padillo, E.U., Webster, M.L., Wheeler, L.A. & Gil, D.W. (2001). alpha(2)-Adrenoceptor agonists inhibit vitreal glutamate and aspartate accumulation and preserve retinal function after transient ischemia. Journal of Pharmacology and Experimental Therapeutics 296, 216–223.Google Scholar
Elena, P.P., Kosina-Boix, M., Denis, P., Moulin, G. & Lapalus, P. (1989). Alpha2-adrenergic receptors in rat and rabbit eye: A tritium-sensitive film autoradiography. Ophthalmic Research 21, 309–314.Google Scholar
Enriquez de Salamanca, A., Siemasko, K.F., Diebold, Y., Calonge, M., Gao, J., Juarez-Campo, M. & Stern, M.E. (2005). Expression of muscarinic and adrenergic receptors in normal human conjunctival epithelium. Investigative Ophthalmology & Visual Science 46, 504–513.Google Scholar
Harrison, J.K., D'Angelo, D.D., Zeng, D.W. & Lynch, K.R. (1991). Pharmacological characterization of rat alpha 2-adrenergic receptors. Molecular Pharmacology 40, 407–412.Google Scholar
Huang, L., Wei, Y.Y., Momose-Hotokezaka, A., Dickey, J. & Okusa, M.D. (1996). Alpha 2B-adrenergic receptors: Immunolocalization and regulation by potassium depletion in rat kidney. American Journal of Physiology 270, F1015–1026.Google Scholar
Huang, Y., Gil, D.W., Vanscheeuwijck, P., Stamer, W.D. & Regan, J.W. (1995). Localization of alpha 2-adrenergic receptor subtypes in the anterior segment of the human eye with selective antibodies. Investigative Ophthalmology & Visual Science 36, 2729–2739.Google Scholar
Kalapesi, F.B., Coroneo, M.T. & Hill, M.A. (2005). Human ganglion cells express the alpha-2 adrenergic receptor: Relevance to neuroprotection. British Journal of Ophthalmology 89, 758–763.Google Scholar
Lafuente, M.P., Villegas-Perez, M.P., Selles-Navarro, I., Mayor-Torroglosa, S., Miralles de Imperial, J. & Vidal-Sanz, M. (2002). Retinal ganglion cell death after acute retinal ischemia is an ongoing process whose severity and duration depends on the duration of the insult. Neuroscience 109, 157–168.Google Scholar
Lafuente, M.P., Villegas-Perez, M.P., Sobrado-Calvo, P., Garcia-Aviles, A., Miralles de Imperial, J. & Vidal-Sanz, M. (2001). Neuroprotective effects of alpha(2)-selective adrenergic agonists against ischemia-induced retinal ganglion cell death. Investigative Ophthalmology & Visual Science 42, 2074–2084.Google Scholar
Lai, R.K., Chun, T., Hasson, D., Lee, S., Mehrbod, F. & Wheeler, L. (2002). Alpha-2 adrenoceptor agonist protects retinal function after acute retinal ischemic injury in the rat. Visual Neuroscience 19, 175–185.Google Scholar
Lee, D.A., Topper, J.E. & Brubaker, R.F. (1984). Effect of clonidine on aqueous humor flow in normal human eyes. Experimental Eye Research 38, 239–246.Google Scholar
Levkovitch-Verbin, H., Harris-Cerruti, C., Groner, Y., Wheeler, L.A., Schwartz, M. & Yoles, E. (2000). RGC death in mice after optic nerve crush injury: Oxidative stress and neuroprotection. Investigative Ophthalmology & Visual Science 41, 4169–4174.Google Scholar
Manns, I.D., Lee, M.G., Modirrousta, M., Hou, Y.P. & Jones, B.E. (2003). Alpha 2 adrenergic receptors on GABAergic, putative sleep-promoting basal forebrain neurons. European Journal of Neuroscience 18, 723–727.Google Scholar
Matsuo, T. & Cynader, M.S. (1992). Localization of alpha-2 adrenergic receptors in the human eye. Ophthalmic Research 24, 213–219.Google Scholar
Maus, T.L., Nau, C. & Brubaker, R.F. (1999). Comparison of the early effects of brimonidine and apraclonidine as topical ocular hypotensive agents. Archive of Ophthalmology 117, 586–591.Google Scholar
Ogidigben, M., Chu, T.C. & Potter, D.E. (1994). Alpha-2 adrenoceptor mediated changes in aqueous dynamics: Effect of pertussis toxin. Experimental Eye Research 58, 729–736.Google Scholar
Osborne, N.N. (1982). Binding of (-)[3H]noradrenaline to bovine membrane of the retina. Evidence for the existence of alpha 2-receptors. Vision Research 22, 1401–1407.Google Scholar
Pow, D.V. & Crook, D.K. (1993). Extremely high titre polyclonal antisera against small neurotransmitter molecules: Rapid production, characterisation and use in light- and electron-microscopic immunocytochemistry. Journal of Neuroscience Methods 48, 51–63.Google Scholar
Pow, D.V. & Hendrickson, A.E. (1999). Distribution of the glycine transporter glyt-1 in mammalian and nonmammalian retinae. Visual Neuroscience 16, 231–239.Google Scholar
Rauen, T., Taylor, W.R., Kuhlbrodt, K. & Wiessner, M. (1998). High-affinity glutamate transporters in the rat retina: A major role of the glial glutamate transporter GLAST-1 in transmitter clearance. Cell Tissue Research 291, 19–31.Google Scholar
Richman, J.G., Brady, A.E., Wang, Q., Hensel, J.L., Colbran, R.J. & Limbird, L.E. (2001). Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin. Journal of Biological Chemistry 276, 15003–15008.Google Scholar
Schadlu, R., Maus, T.L., Nau, C.B. & Brubaker, R.F. (1998). Comparison of the efficacy of apraclonidine and brimonidine as aqueous suppressants in humans. Archive of Ophthalmology 116, 1441–1444.Google Scholar
Serle, J.B., Steidl, S., Wang, R.F., Mittag, T.W. & Podos, S.M. (1991). Selective alpha 2-adrenergic agonists B-HT 920 and UK14304-18. Effects on aqueous humor dynamics in monkeys. Archive of Ophthalmology 109, 1158–1162.Google Scholar
Stone, L.S., Broberger, C., Vulchanova, L., Wilcox, G.L., Hokfelt. T., Riedl. M.S. & Elde, R. (1998). Differential distribution of alpha2A and alpha2C adrenergic receptor immunoreactivity in the rat spinal cord. Journal of Neuroscience 18, 5928–5937.Google Scholar
Toris, C.B., Gleason, M.L., Camras, C.B. & Yablonski, M.E. (1995). Effects of brimonidine on aqueous humor dynamics in human eyes. Archive of Ophthalmology 113, 1514–1517.Google Scholar
Vidal-Sanz, M., Lafuente, M.P., Mayor-Torroglosa, S., Aguilera, M.E., Miralles de Imperial, J. & Villegas-Perez, M.P. (2001a). Brimonidine's neuroprotective effects against transient ischaemia-induced retinal ganglion cell death. European Journal of Ophthalmology 11, S36–S40.Google Scholar
Vidal-Sanz, M., Lafuente, M.P., Mayor, S., de Imperial, J.M. & Villegas-Perez, M.P. (2001b). Retinal ganglion cell death induced by retinal ischemia. neuroprotective effects of two alpha-2 agonists. Survey of Ophthalmology 45, S261–S267.Google Scholar
Wen, R., Cheng, T., Li, Y., Cao, W. & Steinberg, R.H. (1996). Alpha 2-adrenergic agonists induce basic fibroblast growth factor expression in photoreceptors in vivo and ameliorate light damage. Journal of Neuroscience 16, 5986–5992.Google Scholar
Wheeler, L.A., Gilm, D.W. & WoldeMussie, E. (2001). Role of alpha-2 adrenergic receptors in neuroprotection and glaucoma. Survey of Ophthalmology 45, S290–S294.Google Scholar
Wheeler, L.A., Lai, R. & WoldeMussie, E. (1999). From the lab to the clinic: Activation of an alpha-2 agonist pathway is neuroprotective in models of retinal and optic nerve injury. European Journal of Ophthalmology 9, S17–S21.Google Scholar
Wheeler, L.A. & WoldeMussie, E. (2001). Alpha-2 adrenergic receptor agonists are neuroprotective in experimental models of glaucoma. European Journal of Ophthalmology 11, S30–S35.Google Scholar
WoldeMussie, E., Ruiz, G., Wijono, M. & Wheeler, L.A. (2001). Neuroprotection of retinal ganglion cells by brimonidine in rats with laser-induced chronic ocular hypertension. Investigative Ophthalmology & Visual Science 42, 2849–2855.Google Scholar
Yoles, E., Wheeler, L.A. & Schwartz, M. (1999). Alpha2-adrenoreceptor agonists are neuroprotective in a rat model of optic nerve degeneration. Investigative Ophthalmology & Visual Science 40, 65–73.Google Scholar
Zarbin, M.A., Wamsley, J.K., Palacios, J.M. & Kuhar, M.J. (1986). Autoradiographic localization of high affinity GABA, benzodiazepine, dopaminergic, adrenergic and muscarinic cholinergic receptors in the rat, monkey and human retina. Brain Research 374, 75–92.Google Scholar