Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day.

GARBARINO-PICO EDUARDO; CARPENTIERI AGATA RITA; CONTIN MARIA ANA; SARMIENTO MARIA INES; BROCCO MARCELA A; PANZETTA PEDRO; ROSENSTEIN RUTH; CAPUTTO BEATRIS; GUIDO MARIO EDUARDO

JOURNAL OF BIOLOGICAL CHEMISTRY

Año: 2004 vol. 279 p. 51172 - 51181

0021-9258

Retinal ganglion cells send visual and circadian informationto the brain regarding the environmental lightdarkcycles. We investigated the capability of retinalganglion cells of synthesizing melatonin, a highly reliablecircadian marker that regulates retinal physiology,as well as the capacity of these cells to function as autonomouscircadian oscillators. Chick retinal ganglioncells presented higher levels of melatonin assessed byradioimmunoassay during both the subjective day inconstant darkness and the light phase of a light-darkcycle. Similar changes were observed in mRNA levelsand activity of arylalkylamine N-acetyltransferase, akey enzyme in melatonin biosynthesis, with the highestlevels of both parameters during the subjective day.These daily variations were preceded by the elevation ofcyclic-AMP content, the second messenger involved inthe regulation of melatonin biosynthesis. Moreover, culturesof immunopurified retinal ganglion cells at embryonicday 8 synchronized by medium exchange synthesizeda [3H]melatonin-like indole from [3H]tryptophan.This [3H]indole was rapidly released to the culture mediumand exhibited a daily variation, with levels peaking8 h after synchronization, which declined a fewhours later. Cultures of embryonic retinal ganglion cellsalso showed self-sustained daily rhythms in arylalkylamineN-acetyltransferase mRNA expression during atleast three cycles with a period near 24 h. These rhythmswere also observed after the application of glutamate.The results demonstrate that chick retinal ganglioncells may function as autonomous circadian oscillatorssynthesizing a melatonin-like indole during the day.