Melatonin Receptor Blockers Enhance Photoreceptor Survival and Function in Light Damaged Rat Retina
Melatonin is an important retinal neurohormone involved in rhythmic photoreceptor metabolism and in regulating the release of retinal dopamine. Systemic administration of melatonin and conditions supporting its synthesis in the retina seem to be related to increased light damage susceptibility. We found that intraocular injection of competitive melatonin receptor antagonists prior to the dark period before bright light exposure resulted in substantial protection of photoreceptors from light damage. Photoreceptor cell structure was much better preserved in antagonist injected eyes and the ERG threshold was approximately 2 log units of intensity lower. Intraocular injection of a number of other compounds which are known to affect endogenous dopamine levels or stimulate or block dopamine receptors did not have a significant effect on the ERG. However, some showed a tendency to reduce or enhance the effect of light damage on the ERG depending on their expected effect on dopamine levels. These results indicate that blocking the action of endogenous melatonin at retinal receptors can protect photoreceptors from damage by light. Further work is needed to investigate a possible role for dopamine in this protection.
KeywordsDopamine Release Retinal Degeneration Light Damage Flash Intensity Endogenous Melatonin
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- 1.P.M. Iuvone, 1996, Orcadian rhythms of melatonin biosynthesis in retinal photoreceptor cells: Signal transduction, interactions with dopamine, and speculations on a role in cell survival, in: Retinal Degeneration and Regeneration, (S. Kato, N.N. Osborne, and M. Tamai, eds.), pp. 3–13, Kugler Publications, Amsterdam/New York.Google Scholar
- 2.J.C. Besharse, P.M. Iuvone, and M.E. Pierce, 1988, Regulation of rhythmic photoreceptor metabolism: a role for post-receptoral neurons, in: Progress in Retinal Research, Volume 7 (N.N. Osborne and G.J. Chader, eds.), pp. 21–61, Pergamon Press, Oxford.Google Scholar
- 13.T. Sugawara, P.A. Sieving, and R.A. Bush, 1998, ERG threshold elevation is quantitatively related to cell loss in light damaged rat:b-wave by a log-linear and STR by a log-log function, ARVO Abstract, Invest. Ophthalmol. Vis. Sci. 39:S978.Google Scholar
- 14.M.L. Dubocovich, M.I. Masana, S. Iacob, and D.M. Sauri, 1997, Melatonin receptor antagonists that differentiate between the human Mella and Mellb recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor, Naunyn-Schmiedebergs Archives of Pharmacology 355:365–375.CrossRefGoogle Scholar
- 16.M.M. La Vail, M.T. Matthes, D. Yasumura, G. Faktorovich, and R. Steinberg, 1997, Histological method to assess photoreceptor light damage and protection by survival factors, in: Degenerative Retinal Diseases, (M.M. La Vail, J.G. Hollyfield, and R.E. Anderson, eds.), pp. 369–384, Plenum Press, New York.Google Scholar
- 18.T. Sugawara, P.A. Sieving, P.M. Iuvone, and R.A. Bush, 1998, The melatonin antagonist luzindole protects retinal photoreceptors from light damage in the rat, Invest. Ophthalmol. Vis. Sci. 39: In press.Google Scholar
- 20.R.A. Bush, C.E. Remé, M. Terman, and A. Malnoë, 1990, Disk shedding and dopamine rhythms under simulated dawn and dusk, ARVO Abs, Invest. Ophthalmol. Vis. Sci. 31:6.Google Scholar
- 22.W. Kolbinger and R. Weiler, 1993, Modulation of endogenous dopamine release in the turtle retina: effects of light, calcium, and neurotransmitters, Vis: Neurosci. 10:1035–1041.Google Scholar
- 24.L.M. Rapp and T.P. Williams, 1980, A parametric study of retinal light damage in albino and pigmented rats, in: The Effects of Constant Light on Visual Processes (T.P. Williams and B.N. Baker, eds.), pp. 135–159, Plenum Press, New York.Google Scholar
- 25.M.M. La Vail, 1976, Survival of some photoreceptor cells in albino rats following long-term exposure to continuous light, Invest. Ophthalmol. Vis. Sci. 15:64–70.Google Scholar
- 26.G. Tosini, S. Doyle, and M. Menaker, 1998, Melatonin synthesis in the rat retina: cellular localiziation and circadian regulation, ARVO ABSTRACTS, Invest. Ophthalmol, Vis. Sci. 39:S236.Google Scholar
- 27.D.A. Redburn and C.K. Mitchell, 1989, Darkness stimulates rapid synthesis and release of melatonin in rat retina, Vista J. Neurosience 3:391–403.Google Scholar