Photic regulation of melatonin in rat retina and the role of proteasomal proteolysis

Abstract

Several investigations have shown that illumination at night reduces melatonin level in the mammalian pineal, but the effect of night illumination on the retina is not known. In this study retinas were cultured in a flow-through apparatus and then were exposed to light at ZT 18. Light exposure reduced melatonin levels to the daytime level within 30 min. The reduction of melatonin levels was due to a rapid decrease in the activity of the enzyme AA-NAT; AA-NAT mRNA levels were not affected by illumination. Pre-incubation with lactacystin (25 microM) prevented light-induced reduction of AA-NAT activity and melatonin levels. These results demonstrate that melatonin levels in the mammalian retina are affected by light exposure at night, via proteosomal proteolysis of AA-NAT.

Gating of the cAMP Signaling Cascade and Melatonin Synthesis by the Circadian Clock in Mammalian Retina

“…The fact that this rhythm shows the three fundamental characteristics of a circadian clock (i.e., free-run, entrainment, and temperature compensation) demonstrates that melatonin synthesis in the retina is controlled by a bona fide circadian clock located within this tissue. In addition to clock control, retinal melatonin levels rapidly (5-10 min) decrease after light exposure at night (Hamm et al, 1983;Fukuhara et al, 2001) to ensure that melatonin is released and acts only in darkness. As in the pineal gland (Gastel et al, 1998), the rapid reduction in melatonin levels is achieved by a rapid decrease in AA-NAT enzyme by proteasomal proteolysis (Fukuhara et al, 2001;Iuvone et al, 2002).…”

“…Perhaps the most intensely investigated of these functions is melatonin biosynthesis, the synthesis of which in retinal photoreceptor cells displays a clear circadian rhythm in vivo and in vitro Cahill and Besharse 1993;Menaker, 1996, 1998). Retinal melatonin is high at night and low during the day, and the changes in melatonin levels are a direct reflection of the change in the rate of transcription and activity of the enzyme arylalkylamine N-acetyltransferase (AA-NAT) Niki et al, 1998;Sakamoto and Ishida, 1998;Fukuhara et al, 2001).…”

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…The regulation of these enzymes is fascinating and much studied (Wurtman and Axelrod, 1968;Cardinali, 1981;Klein, 1999Klein, , 2007Olcese, 1999). Most recently, molecular approaches are revealing the transcriptional and posttranscriptional mechanisms responsible for daily fluctuations in AA-NAT (Borjigin et al, 1995(Borjigin et al, , 1999Roseboom et al, 1996;Gastel et al, 1998;Klein, 1999;Fukuhara et al, 2001) and regulation of HIOMT (Gauer and Craft, 1996). Use of sensitive RT-PCR techniques suggests that low levels of AA-NAT and HIOMT, and therefore local melatonin synthesis, may also occur in other tissues, such as gut, testis, spinal cord, raphe nucleus, and striatum (Stefulj et al, 2001).…”

Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor

“…In a few cases, the circadian pacemaker driving rhythmic melatonin synthesis has been localized to the photoreceptors themselves (2,4,5). In the retina melatonin levels are high during the night and low during the day and exposure to light during the night induces a rapid and dramatic decrease in the levels of melatonin (6,7). Retinal melatonin synthesis is directly controlled by the circadian clock via E-box mediated transcription (8) and via the gating of the cAMP signaling cascade (9).…”