Abstract
Purpose :
Our work in rodents has demonstrated a potential role for the orexin neurotransmitter system in the regulation of intraocular pressure (IOP). However, the tree shrew (Tupaia belangeri) is a para-primate and a potentially better animal model for certain glaucoma investigations given its stronger similarities to the human in the anterior chamber and optic nerve head. Although we know orexins are expressed in the hypothalamus of the tree shrew, orexin expression within the glaucomatous tree shrew brain has not been reported. Purpose: to histologically identify and characterize orexin A in the glaucomatous tree shrew brain.
Methods :
Experimental glaucoma was induced by bead occlusion in the anterior chamber. After 4 weeks of outflow occlusion and sustained ocular hypertension, brains were fixed and coronally sectioned at 30 microns then incubated with fluorescently labeled polyclonal anti-orexin A antibodies.
Results :
Each of the 3 brains demonstrated dense, cellular expression of orexin A in the cytoplasm of neurons within the dorsomedial hypothalamus and within the adjacent lateral hypothalamus near the fornix (DMH/LH). In addition, orexin A was detected in axons extending into the thalamic paraventricular nucleus (PVT) where anti-cFos immunoreactivity was strong.
Conclusions :
Tree shrews with experimental ocular hypertension displayed dense cellular orexin A within the DMH/LH region of the brain as well as axonal orexin A within the PVT nucleus where localized, strong cellular activity was also evident. These data identify the orexins, the DMH/LH, and the PVT as potential CNS targets for further study and possible therapeutic intervention in the glaucoma tree shrew model.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.