Both dopamine and melatonin are important for the regulation of retinal rhythmicity, and substantial evidence suggests that these two substances are mutually inhibitory factors that act as chemical analogs of day and night. A circadian oscillator in the mammalian retina regulates melatonin synthesis. Here we show a circadian rhythm of retinal dopamine content in the mouse retina, and examine the role of melatonin in its control. Using high-performance liquid chromatography (HPLC), we measured levels of dopamine and its two major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in retinas of C3H+/+ mice (which make melatonin) and C57BL/6J mice that are genetically incapable of melatonin synthesis. In a light/dark cycle both strains of mice exhibited daily rhythms of retinal dopamine, DOPAC, and HVA content. However, after 10 days in constant darkness (DD), a circadian rhythm in dopamine levels was present in C3H, but not in C57 mice. C57 mice given ten daily injections of melatonin in DD exhibited a robust circadian rhythm of retinal dopamine content whereas no such rhythm was present in saline-injected controls. Our results demonstrate that (1) a circadian clock generates rhythms of dopamine content in the C3H mouse retina, (2) mice lacking melatonin also lack circadian rhythms of dopamine content, and (3) dopamine rhythms can be generated in these mice by cyclic administration of exogenous melatonin. Our results also indicate that circadian rhythms of retinal dopamine depend upon the rhythmic presence of melatonin, but that cyclic light can drive dopamine rhythms in the absence of melatonin.
1. Current knowledge of the mechanisms of circadian and photic regulation of retinal melatonin in vertebrates is reviewed, with a focus on recent progress and unanswered questions. 2. Retinal melatonin synthesis is elevated at night, as a result of acute suppression by light and rhythmic regulation by a circadian oscillator, or clock, which has been localized to the eye in some species. 3. The development of suitable in vitro retinal preparations, particularly the eyecup from the African clawed frog, Xenopus laevis, has enabled identification of neural, cellular, and molecular mechanisms of retinal melatonin regulation. 4. Recent findings indicate that retinal melatonin levels can be regulated at multiple points in indoleamine metabolic pathways, including synthesis and availability of the precursor serotonin, activity of the enzyme serotonin N-acetyltransferase, and a novel pathway for degradation of melatonin within the retina. 5. Retinal dopamine appears to act through D2 receptors as a signal for light in this system, both in the acute suppression of melatonin synthesis and in the entrainment of the ocular circadian oscillator. 6. A recently developed in vitro system that enables high-resolution measurement of retinal circadian rhythmicity for mechanistic analysis of the circadian oscillator is described, along with preliminary results that suggest its potential for elucidating general circadian mechanisms. 7. A model describing hypothesized interactions among circadian, neurochemical, and cellular mechanisms in regulation of retinal melatonin is presented.
Vertebrate retinal photoreceptors periodically shed membrane from their outer segment distal tips; this material is phagocytosed and degraded by the retinal pigmented epithelium. Both a circadian oscillator and the daily light-dark cycle affect disk shedding, and the effects of both may be mediated by melatonin. To clarify melatonin's role in this process, we asked whether endogenous melatonin is required for rhythmic disk shedding in mouse retina. We analyzed disk shedding in two mouse strains: C3H, which produce melatonin in retina and pineal under the control of circadian oscillators, and C57BL/6, which do not produce melatonin. In cyclic light, both strains exhibited a robust cycle of disk phagosome content in the pigmented epithelium. Peak shedding occurred just after dawn, and trough levels occurred during the middle of the dark phase. In constant darkness, mice exhibited circadian rhythms of locomotor activity, the characteristics of which were similar between strains. Both strains also exhibited rhythmic disk shedding in constant darkness, although amplitudes of the rhythms were damped. Exogenous melatonin delivered once per day failed to reestablish high-amplitude cyclic shedding in mice held in constant darkness. Our results show that, while disk shedding in cyclic light is robustly rhythmic, neither rhythmic production of melatonin nor the circadian oscillator responsible for rhythmic locomotor activity is sufficient to drive high-amplitude rhythmic shedding in constant darkness. More importantly, melatonin is required neither for cyclic changes in the rate of disk shedding in cyclic light, nor for the circadian rhythm of disk shedding in constant darkness.
The Atlantic tarpon, Megalops atlanticus, is a large piscivorous fish that supports economically important recreational fisheries in the Gulf of Mexico, Caribbean, and Florida Atlantic coast. Megalops atlanticus undergoes ontogenetic shifts in morphology, hatching in the open ocean as larvae (less than 1 cm in length), moving into hypoxic turbid mangrove marshes as juveniles (around 10 cm in length), and then moving into coastal oceanic waters as adults (over 100 cm in length). In this study, photoreceptor distributions, opsin distributions, and photoreceptor absorbance characteristics were studied with light microscopy, transmission electron microscopy, antiopsin immunofluorescence, and microspectrophotometry, respectively, at four ecologically distinct life-history stages--premetamorphic larva, settlement stage, juvenile, and adult. The purposes of this study were 1) to determine the extent to which the retina of M. atlanticus changes over the course of development and 2) to relate these retinal changes with ecological shifts between developmental stages. The new data presented here indicate that the M. atlanticus retina changes substantially in rod and cone distributions and absorbance characteristics over the course of development and that these changes correlate closely with those in habitat and behavior. We show that M. atlanticus has a rod-dominated retina at the larval stage (which is unusual for teleost larvae) and that the scotopic visual system becomes far better developed with maturity, adding a substantial tapetum and high densities of small, bundled, and stacked rod cells. We also show that there are shifts in cone and rod spectral sensitivities and an increase in the diversity of spectrally distinct cone classes, including the addition of ultraviolet cones as fish mature into adults.
The classical understanding of mammalian vision is that it occurs through "duplex" retinae containing both rod and cone photoreceptors, the signals from which are processed through rod- and/or cone-specific signaling pathways. The recent discovery of rod monochromacy in some cetacean lineages provides a novel opportunity to investigate the effects of an evolutionary loss of cone photoreception on retinal organization. Sequence analysis of right whale (Eubalaena glacialis; family Balaenidae) cDNA derived from long-wavelength sensitive (LWS) cone opsin mRNA identified several mutations in the opsin coding sequence, suggesting the loss of cone cell function, but maintenance of non-photosensitive, cone opsin mRNA-expressing cells in the retina. Subsequently, we investigated the retina of the closely related bowhead whale (Balaena mysticetus; family Balaenidae) to determine how the loss of cone-mediated photoreception affects light signaling pathways in the retina. Anti-opsin immunofluorescence demonstrated the total loss of cone opsin expression in B. mysticetus, whereas light microscopy, transmission electron microscopy, and bipolar cell (protein kinase C-α [PKC-α] and recoverin) immunofluorescence revealed the maintenance of cone soma, putative cone pedicles, and both rod and cone bipolar cell types. These findings represent the first immunological and anatomical evidence of a naturally occurring rod-monochromatic mammalian retina, and suggest that despite the loss of cone-mediated photoreception, the associated cone signaling structures (i.e., cone synapses and cone bipolar cells) may be maintained for multichannel rod-based signaling in balaenid whales. J. Comp. Neurol. 524:2873-2885, 2016. © 2016 Wiley Periodicals, Inc.
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