Effect of orbital enucleation on glucose homeostasis and morphology of the suprachiasmatic nucleus.

In rats there is a direct neural connection called the retinohypothalamic tract (RHT) from retinal ganglion cells to the ventrolateral part of the suprachiasmatic nucleus (SCN), which has neurons containing vasoactive intestinal polypeptide (VIP)-like substance. Previously, we observed that bilateral orbital enucleation (blinding) caused temporary suppression of the hyperglycemic response to intracranial injection of 2-deoxy-D-glucose (2DG) from week 4 to 6 after blinding. Moreover, bilateral lesions of the SCN had a similar effect. From these findings, we supposed that the neurons responsible for the hyperglycemic response to 2DG were present in the SCN, that after blinding these neurons temporarily lost their activity, and that this functional change was reflected in the morphology of the SCN. To investigate this possibility, we examined the morphological changes of the SCN by Nissl staining and immunohistochemical studies with anti-VIP and anti-peptide histidine isoleucine (PHI) antibodies in blinded rats, and the relationship between these morphological changes and the hyperglycemic response to 2DG. After surgical blinding, we observed following changes. (1) The optic chiasm became thinner. (2) The SCN became displaced rostrally. (3) The density of neurons in the middle to caudal part of the SCN, where the retinal ganglion cells projected, decreased markedly without change in cell number during the period when the hyperglycemic response to intracranial injection of 2DG was temporarily suppressed after blinding. The first and second changes seemed to reflect reduction of fibers and axon terminals of retinal ganglion cells and their innervation, respectively. As the third change was parallel with suppression of the hyperglycemic response to 2DG injection, it may reflect functional change of the neurons in the SCN that are responsible for the hyperglycemia due to 2DG.