Early-Stage Retinal Melatonin Synthesis Impairment in Streptozotocin-Induced Diabetic Wistar Rats

Autor(es)

Buonfiglio, Daniella do Carmo ^[1] ; Peliciari-Garcia, Rodrigo Antonio ^[1] ; do Amaral, Fernanda Gaspar ^[1] ; Peres, Rafael ^[1] ; Araujo Nogueira, Tatiane C. ^[1] ; Afeche, Solange Castro ^[2] ; Cipolla-Neto, Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Butantan Inst, Lab Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE; v. 52, n. 10, p. 7416-7422, SEP 2011.
• Citações Web of Science: 27

Resumo

PURPOSE. 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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. (Invest Ophthalmol Vis Sci. 2011;52:7416-7422) DOI:10.1167/iovs.10-6756 (AU)

• Processo FAPESP: 04/06767-2 - O papel da melatonina no controle do metabolismo energético: interações hormonais, ações centrais e periféricas (pineal, obesidade, diabetes e envelhecimento)
• Beneficiário: José Cipolla Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/52920-0 - O papel da melatonina no controle do metabolismo energético: ações centrais, periféricas e a regulação circadiana da função metabólica pineal, diabetes, obesidade e envelhecimento
• Beneficiário: José Cipolla Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático