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Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats

Retinal melatonin synthesis occurs in the photoreceptor layer in a circadian manner, controlling several physiologic rhythmic phenomena, besides being the most powerful natural free radical scavenger. The purpose of the present work was to evaluate the diurnal profile of retinal melatonin content an...

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Published in:Investigative ophthalmology & visual science 2011-09, Vol.52 (10), p.7416-7422
Main Authors: do Carmo Buonfiglio, Daniella, Peliciari-Garcia, Rodrigo Antonio, do Amaral, Fernanda Gaspar, Peres, Rafael, Nogueira, Tatiane C Araujo, Afeche, Solange Castro, Cipolla-Neto, José
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container_title Investigative ophthalmology & visual science
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creator do Carmo Buonfiglio, Daniella
Peliciari-Garcia, Rodrigo Antonio
do Amaral, Fernanda Gaspar
Peres, Rafael
Nogueira, Tatiane C Araujo
Afeche, Solange Castro
Cipolla-Neto, José
description Retinal melatonin synthesis occurs in the photoreceptor layer in a circadian manner, controlling several physiologic rhythmic phenomena, besides being the most powerful natural free radical scavenger. The purpose of the present work was to evaluate the diurnal profile of retinal melatonin content and the regulation of its synthesis in the retina of streptozotocin-induced diabetic rats. Diabetes was induced in male Wistar rats (12 hour-12 hour light/dark cycle) with streptozotocin. Control, diabetic, and insulin-treated diabetic animals were killed every 3 hours throughout the light-dark cycle. Retinal melatonin content was measured by high-performance liquid chromatography, arylalkylamine N-acetyltransferase (AANAT) activity was analyzed by radiometric assay, Bmal1 gene expression was determined by qPCR, and cyclic adenosine monophosphate (cAMP) content was assessed by ELISA. Control animals showed a clear retinal melatonin and AANAT activity daily rhythm, with high levels in the dark. Diabetic rats had both parameters reduced, and the impairment was prevented by immediate insulin treatment. In addition, the Bmal1 expression profile was lost in the diabetic group, and the retinal cAMP level was reduced 6 hours after lights on and 3 hours after lights off. The present work shows a melatonin synthesis reduction in diabetic rats retinas associated with a reduction in AANAT activity that was prevented by insulin treatment. The Bmal1-flattened gene expression and the cAMP reduction seem to be responsible for the AANAT activity decrease in diabetic animals. The melatonin synthesis reduction observed in the pineal gland of diabetic rats is also observed in a local melatonin tissue synthesizer, the retina.
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subjects Animals
ARNTL Transcription Factors - genetics
Arylalkylamine N-Acetyltransferase - metabolism
Cell Survival
Chromatography, High Pressure Liquid
Circadian Rhythm - physiology
Cyclic AMP - metabolism
Diabetes Mellitus, Experimental - metabolism
Diabetic Retinopathy - metabolism
DNA Fragmentation
Enzyme-Linked Immunosorbent Assay
Gene Expression
Male
Melatonin - biosynthesis
Pineal Gland - surgery
Polymerase Chain Reaction
Radiometry
Rats
Rats, Wistar
Retina - metabolism
title Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats
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