Rhythmic regulation of retinal melatonin: Metabolic pathways, neurochemical mechanisms, and the ocular circadian clock

Cahill, Gregory M.; Grace, Michael S.; Besharse, Joseph C.

doi:10.1007/bf00734814

Cited by 157 publications

(74 citation statements)

References 158 publications

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“…Expression follows a daily rhythm, which is driven by an endogenous clock in photoreceptors cells (Cahill et al, 1991;Tosini and Menaker, 1996;Tosini, 2000;Falcón et al, 2003). AANAT functions to control melatonin synthesis in some vertebrate retinas; however, it has been proposed that it also plays a role in the retina in arylalkylamine detoxification (Coon et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Coon

Klein

2006

Molecular and Cellular Endocrinology

106

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The melatonin rhythm-generating enzyme, arylalkylamine N-acetyltransferase (AANAT) is known to have recognizable ancient homologs in bacteria and fungi, but not in other eukaryotes. Analysis of new cDNA and genomic sequences has identified several additional homologs in other groupings. First, an AANAT homolog has been found in the genome of the cephalochordate amphioxus, representing the oldest homolog in chordates. Second, two AANAT homologs have been identified in unicellular green algae. The homologs in amphioxus, unicellular green algae, fungi and bacteria are similarly primitive in that they lack sequences found in vertebrate AANATs that are involved in regulation and that facilitate binding and catalysis. In addition, all these sequences are intronless. These features are consistent with horizontal transfer of the AANAT ancestor from bacteria to green algae, fungi and chordates. Lastly, a third AANAT gene has been found in teleost fish, suggesting that AANAT genes serve multiple functions in addition to melatonin synthesis.

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Section: Introductionmentioning

confidence: 99%

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Coon

Klein

2006

Molecular and Cellular Endocrinology

106

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“…Melatonin is synthesized rhythmically-with increased production at night-in most vertebrate retinas (Olcese and Møller, 1989;Cahill et al, 1991;Zawilska and Nowak, 1992;Cahill and Besharse, 1995). Several lines of evidence from multiple species indicate that melatonin is synthesized by retinal photoreceptors (Bubenik et al, 1976(Bubenik et al, , 1978Klein et al, 1996Klein et al, , 1997Niki et al, 1998;Wiechmann and Hollyfield, 1989).…”

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confidence: 99%

“…Several lines of evidence from multiple species indicate that melatonin is synthesized by retinal photoreceptors (Bubenik et al, 1976(Bubenik et al, , 1978Klein et al, 1996Klein et al, , 1997Niki et al, 1998;Wiechmann and Hollyfield, 1989). The indole may act as a circadian regulator of several retinal rhythms (Pierce and Besharse, 1986;Besharse et al, 1988;Cahill et al, 1991;Zawilska and Nowak, 1992). Melatonin mimics darkness by causing aggregation of melanin pigment granules in the retinal pigment epithelium (Pang and Yew, 1979), activating disk shedding in rod photoreceptors (Besharse and Dunis, 1983), and elongating cone photoreceptors Besharse, 1985, 1987).…”

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confidence: 99%

Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

Calderón¹,

Mohamed²,

Muñoz³

et al. 2002

Anat. Rec.

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Given that the local melatonin levels exhibit rhythmic daily changes in the retina of the viscacha, we considered it important to study the likely daily variations in morphology and specific 2-[ 125 I]-iodomelatonin binding in retinas from this rodent and to correlate these putative changes with local indole levels. Adult animals of both sexes were captured in their habitat and were kept under a natural photoperiod. For light and electron microscopic studies the viscachas were sacrificed by decapitation at 08:00, 16:00, and 24:00 hr. A computer-assisted image analysis system was used to measure the thickness of the complete retina, the photoreceptor layer, the rod outer and inner segments, and the outer nuclear layer. The daily variation in 2-[ 125 I]-iodomelatonin binding sites was followed during a 24-hr light-dark cycle, the animals being sacrificed at six time points. The parameters studied showed significant variations throughout the 24-hr period. Maximal specific binding, lysosomal content in the pigment epithelium, and photoreceptor layer outer segment thicknesses were observed at 24:00 hr. Close contact between photoreceptor membranes and microvilli of the pigment epithelium was observed at 08:00 and 16:00 hr. Moreover, the minimal outer segment thickness at 16:00 hr was accompanied by a scarcity of dense bodies, such as lysosomes, a maximum dispersion of melanin pigment granules, and a minimum density of radioligand binding sites. Therefore, in the retina of the viscacha, we suggest that the interaction between melatonin and specific sites could be one of the factors or causes that participate in the regulation of the daily morphological changes observed in viscacha.

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“…The change from rod to cone vision is a complex process involving diurnal and circadian rhythms. Vertebrate retinas contain a circadian clock (Cahill et al, 1991;Tosini and Menaker, 1996). Among other functions, it governs melatonin synthesis, which in turn helps to regulate the production and release of dopamine (for review see Cahill and Besharse, 1995).…”

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confidence: 99%

Diurnal and circadian variation of protein kinase C immunoreactivity in the rat retina

Gábriel

LeSauter

Silver

et al. 2001

J of Comparative Neurology

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We studied the dependence of the expression of protein kinase C immunoreactivity (PKC-IR) in the rat retina on the light:dark (LD) cycle and on circadian rhythmicity in complete darkness (DD). Two anti-PKC alpha antibodies were employed: One, which we call PKCαβ recognized the hinge region; the other, here termed PKCα, recognized the regulatory region of the molecule. Western blots showed that both anti-PKC antibodies stained an identical single band at approximately 80 kD. The retinal neurons showing PKC-IR were rod bipolar cells and a variety of amacrine neurons. After 3 weeks on an LD cycle, PKCαβ-IR in both rod bipolar and certain amacrine cells manifested a clear rhythm with a peak at zeitgeber time (ZT) of 06-10 hours and a minimum at ZT 18. No rhythm in total PKC-IR was observed when using the PKCα antibody, but, at ZT 06-10 hours, rod bipolar axon terminals showed increased immunostaining. After 48 hours in DD, with either antibody, rod bipolar cells showed increased PKC-IR. The PKCα antibody alone revealed that, after 48 hours, AII amacrine neurons, which lacked PKC-IR in an LD cycle, manifested marked PKC-IR, which became stronger after 72 hours. Light administered early in the dark period greatly increased PKCαβ-IR in rod bipolar and some amacrine neurons. Our data indicate that light and darkness exert a strong regulatory influence on PKC synthesis, activation, and transport in retinal neurons. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe daily light:dark cycle (LD) is a fundamental regulator of retinal activity. Most retinas have duplex function, meaning that rod photoreceptors and their associated circuitry are specialized for nocturnal vision, whereas cone photoreceptors and their circuits govern retinal function in bright light. The change from rod to cone vision is a complex process involving diurnal and circadian rhythms. Vertebrate retinas contain a circadian clock (Cahill et al., 1991;Tosini and Menaker, 1996). Among other functions, it governs melatonin synthesis, which in turn helps to regulate the production and release of dopamine (for review see Cahill and Besharse, 1995). The rhythms of melatonin and dopamine are in counterphase (Adachi et al., 1998), and these two intrinsic retinal neurochemicals are messengers for darkness and light, respectively (Cahill et al., 1991). The production of certain retinal proteins, for example, iodopsin (Pierce et al., 1993) and tryptophan hydroxylase (Green et al., 1995), also appears to be regulated by a circadian rhythm. Perhaps only a few critical proteins are directly under the control of the circadian clock; Green and Besharse (1996) found that only four of 2,000 retinal mRNAs examined showed a circadian rhythm of expression. Several important retinal activities also manifest a circadian rhythm, including photoreceptor outer segment disk shedding (La Vail, 1976), retinomotor movements (Levinson and Burnside, 1981), visual pigment synthesis (Von Schantz et al., 1999), relative expression of rod and cone signa...

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Rhythmic regulation of retinal melatonin: Metabolic pathways, neurochemical mechanisms, and the ocular circadian clock

Cited by 157 publications

References 158 publications

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

Diurnal and circadian variation of protein kinase C immunoreactivity in the rat retina

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