Altered morphology of rod bipolar cell axonal terminals in the retinas of mice carrying genetic deletion of somatostatin subtype receptor 1 or 2.

Abstract

Somatostatin (SRIF), similar to other neuropeptides, is likely to influence the morpho-functional characteristics of neurons. We studied possible morphological alterations of mouse retinal neurons following genetic deletion of SRIF subtype receptor 1 [sst1 knockout (KO)] or 2 (sst2 KO). In sst1 KO retinas, axonal terminals of rod bipolar cells (RBCs), identified with protein kinase C immunoreactivity, were 25% larger than in controls. In contrast, in sst2 KO retinas, RBC axonal terminals were significantly smaller (-14%). No major ultrastructural differences were observed between control and KO RBCs. In sst2 KO retinas, SRIF levels decreased by about 35%, while both sst1 receptor mRNA and protein increased by about 170% and 100%, respectively. This compares to previous results reporting an increase of both retinal SRIF and sst2 receptors following sst1 receptor deletion. Together, these findings suggest that, on the one hand, sst1 receptor deletion induces over-expression of sst2 receptors, and vice versa; on the other hand, that an imbalance in sst1 and sst2 receptor expression and/or changes in the levels of retinal SRIF induced by sst1 or sst2 receptor deletion are responsible for the morphological changes in RBC axonal terminals. Similar alterations of RBC terminals were observed in KO retinas at 2 weeks of age (eye opening). In addition, reverse transcription-polymerase chain reaction analysis of the expression of sst2 and sst1 receptors in developing sst1 and sst2 KO retinas, respectively, demonstrated that these receptors are up-regulated at or near eye opening. These findings suggest that the integrity of the somatostatinergic system during development is necessary for proper RBC maturation.