Downregulation of the atrial natriuretic peptide/natriuretic peptide receptor-C system in the early stages of diabetic retinopathy in the rat.

PURPOSE Atrial natriuretic peptide (ANP) is a known vascular antipermeability and antiangiogenic factor, but its possible alteration during the early stages of diabetic retinopathy has not yet been explored. The present study sought to investigate the expression of ANP and its receptors using a model of streptozotocin (STZ) induced diabetes in the rat. METHODS Diabetes was induced in male Wistar rats by an intraperitoneal injection of STZ. Age matched animals served as control. One and 3 months after the onset of diabetes, the expression of ANP mRNA and that of its receptors (NPRA, NPRB, NPRC) and the immunoreactive ANP was quantified in retinal tissue by quantitative real time reverse transcription-polymerase chain reaction (RT-PCR) and radioimmunoassay, respectively. The locations of ANP and glial fibrillary acidic protein (GFAP) in normal and diabetic retinas were also established by immunohistochemistry. RESULTS No alteration in the gene expression of the retinal natriuretic peptide system was noted after 1 month of diabetes. However, 3 months after the onset of diabetes, significantly diminished ANP and NPRC mRNA levels were detected in the retina of diabetic rats compared to controls, while NPRA, NPRB mRNA levels remained unchanged. At this time point, retinal ANP concentrations were significantly diminished in the diabetic rats compared to control rats. However, at 1 month retinal ANP concentrations in diabetic retina were similar to control rats. Diabetes caused the downregulation of ANP protein expression in the layers of the retina at 3 months after the induction of diabetes. ANP immunoreactivity was detected in the cell bodies of the astrocytes and in their processes enveloping vessels. CONCLUSIONS The downregulation of ANP and NPRC in retinas of diabetic rats suggests a role for this peptide in experimental diabetic retinopathy. Further studies should address the possible involvement of the ANP/NPRC system in the pathophysiology of diabetic retinopathy.