title: Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats.
abstract: OBJECTIVE
  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.
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Daniella
authors: D
authors: do Carmo Buonfiglio
authors: Rodrigo Antonio
authors: RA
authors: Peliciari-Garcia
authors: Fernanda Gaspar
authors: FG
authors: do Amaral
authors: Rafael
authors: R
authors: Peres
authors: Tatiane C Araujo
authors: TC
authors: Nogueira
authors: Solange Castro
authors: SC
authors: Afeche
authors: José
authors: J
authors: Cipolla-Neto
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000378:metabolism; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D053938:DNA Fragmentation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D010870:Pineal Gland / Q000601:surgery; D016133:Polymerase Chain Reaction; D011874:Radiometry; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; D000242:Cyclic AMP; C520223:Aanat protein, rat; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin