Abstract
Abstract: :
Purpose: New agents are being developed for in vivo imaging of amyloid, a component of senile plaques thought to contribute to pathophysiology in Alzheimer's disease (PNAS 97:7609; Nucl Med Biol 30:573). These soluble dyes cross the blood–brain barrier after IV injection and bind to amyloid, allowing fluorescent imaging or detection by SPECT, PET, or MRI. Given that amyloid is elevated in rat retinas with chronic ocular hypertension (COH), we determined if such dyes could image ocular or brain structures damaged by COH. Methods: 5 brown Norway rats were treated in the right eye to induce COH by limbal injection of hypertonic (2.0 M) saline. IOP was recorded weekly with a calibrated Tonopen XL. After increasing levels of IOP exposure were reached, animals were sedated. Two separate IV tail vein injections of K–114 dye (0.2% in DMSO/EtOH) were performed 12 hours apart in rats with moderate to severe COH in the right eye. The left eyes served as normotensive controls. Retinas, optic nerves and brains were obtained and cryosectioned 6 hours after the second K–114 injection. Sections were examined under fluorescent microscopy and digitally imaged (KS400 imaging system, Zeiss). Results: Fluorescent labeling of amyloid was noted in inner and outer retinal cells and in optic nerve heads of COH rats but not in controls. Extensive labeling of amyloid deposits was noted in COH optic nerves, while control nerves showed no labeling. In COH nerves with mild IOP exposure, amyloid labeling was confined to the lamina cribrosa. In COH nerves with severe IOP exposure, labeling was seen throughout the laminar and retrolaminar optic nerve. Imaging of the right superior colliculus (SC), target for 90% uncrossed RGCs from the COH eye, showed extensive labeling of amyloid. The left SC, target for 10% crossed RGCs from the COH eye, showed moderate labeling. Conclusions: K–114 successfully imaged amyloid deposits in the eye and brain of COH rats after IV injection. In COH nerves, amyloid deposition occurs initially at the lamina cribrosa and proceeds in an anterograde direction toward the brain. This study points to a number of potential clinical applications. IVFA or adaptive optics using K–114 or SPECT using 125I K–114 could be used to perform non–invasive in vivo imaging of RGCs, optic nerves, or brain of glaucoma patients. In–vivo imaging could assess for glaucomatous damage much earlier than other modalities, and as a longitudinal function of amyloid buildup.
Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • intraocular pressure • ganglion cells