Unique Regulation of the Melatonin Synthetic Pathway in the Retina of Diurnal FemaleArvicanthis ansorgei(Rodentia)

Abstract

Knowledge about melatonin synthesis and its potential roles within the retina remains fragmented, especially in mammals where studies have focused on the penultimate enzyme of melatonin synthesis arylalkylamine N-acetyltransferase (AA-NAT), whereas the final enzyme necessary for melatonin production is hydroxyindole-O-methytransferase (HIOMT). We explored multiple parameters of the melatonin synthetic pathway in the cone-rich retina of a diurnal rodent, Arvicanthis ansorgei, cones being previously implicated as probable reservoirs of melatonin production. We analyzed the temporal and spatial expression of Aa-nat mRNA and AA-NAT protein and enzymatic activity of AA-NAT, HIOMT, as well as the melatonin receptor type 1 and melatonin itself. We report that Aa-nat mRNA was localized principally to cones and ganglion cells (retinal ganglion cell [RGC]) with opposing cyclic expression, being maximal in cones during the night, and maximal in RGC in the daytime. AA-NAT protein was also immunolocalized to these same populations, and was present and active throughout the 24-hour period. HIOMT immunolocalization mirrored that of AA-NAT, but expression levels and activity were extremely low and remained uniform throughout the 24-hour period. MT1 showed a complementary expression pattern to the synthetic enzymes, present in rod photoreceptors, some inner retinal neurons and RGC. Surprisingly, melatonin levels were consistently low throughout the day/night cycle, in accordance with the low activity levels of HIOMT. These data demonstrate that the melatonin synthetic pathway in a diurnal rodent differs from that described for other tissues and species (nocturnal and diurnal), the contrasting phase expression in photoreceptors and RGC, suggesting distinct roles in these populations.

Ocular Clocks: Adapting Mechanisms for Eye Functions and Health

“…It should be mentioned that melatonin regulation in the diurnal rodent Arvicanthis appears to be bimodal, with one source (cones) peaking in the night and a second source (ganglion cells) peaking in the day. 167 Finally, it is worthwhile mentioning that although melatonin is present in the primate retina, it is not clear whether melatonin found in the eye is actually synthesized in situ or is of pineal origin. 168 …”

Diversity and evolution of African Grass Rats (Muridae:Arvicanthis)—From radiation in East Africa to repeated colonization of northwestern and southeastern savannas

“…They are major agricultural pests, as their reproductive success (especially after annual dry‐season depletion) makes them more successful than other competing rodents (Sicard, Diarra, & Cooper, ). Because most species are diurnal and easy to breed, Arvicanthis became a popular model also in physiological research, especially in studies of circadian rhythms, vision, and endocrinology (Castillo‐Ruiz, Indic, & Schwartz, ; Gianesini, Clesse, Tosini, Hicks, & Laurent, ; Langel, Smale, Esquiva, & Hannibal, ).…”

Hydroxyindole-O-methyltransferase (HIOMT) activity in the retina of melatonin-proficient mice

“…Our results from dark- and light-adapted isolated retinas provide additional support for the presence of a photosensitive two-step (AANAT/HIOMT) biosynthesis of MLT in the mouse retina: 90 min light exposure leads to a rapid decrease in both NAS and MLT retinal levels. This finding represents a starting point to define the modulation of retinal HIOMT function by light, circadian clock or catecholamine release vs. the pineal ones (Ribelayga et al., 1999; Baba et al., 2009, 2013; Gianesini et al., 2015). One open issue waiting for clarification is the homeostasis of the retinal milieu, and its alteration in eye pathologies (Samples et al., 1988; Alcantara-Contreras et al., 2011; Blasiak et al., 2016).…”