Abstract
The retinal remodeling is known in a human inherited disease, retinitis pigmentosa (RP), which leads to the loss of vision caused by photoreceptor degeneration. It has been reported in the Royal College of Surgeons (RCS) rat which is one of animal models for studying human retinitis pigmentosa that the degenerated photoreceptors cause a dramatic reorganization of retina, including the inner nuclear layer and the ganglion cell layer, at later stages in the RCS rat. At present treatments for restoring vision in RP founded on the intact properties of remaining neurons, and the remodeling of retinal degeneration at later stages were neglected. However, the morphological features of retinal ganglion cells (RGCs) in the RCS rat at later stages of degeneration have not been carefully studied. Therefore, the goals of this study were to characterize the properties of RGCs at later stages in morphology and electrophysiology. In the present study, we characterized morphological properties of RGCs in two aged groups of RCS rats (P331-418 and P526-575) and two strains of normal rats (SD and LE). In addition, examination of the physiological properties of RGCs in SD and RCS rats was also attempted. The responses of RGCs upon light and electrical stimulations in SD rats, and those upon electrical stimulation in RCS rats were recorded. Microinjection with Neurobiotin was used to assess the dendritic morphologies and coupling patterns of RGCs. In collaboration with Prof. CY Wu (National Chiao Tung University) in retinal prosthesis program, the electrical stimulation was provided by activating a silicone-based microphotodiode array with a 532 nm laser from the subretinal side. Although we did not find RGC responses upon electrical stimulation in the RCS rat, the morphological features of RGCs, including total dendritic length, number of branching points, appearance of dendritic beads, and tracer coupling patterns in the RCS rats were significantly different from those in the normal rats. The finding indicates that RGCs in the RCS rat may undergo significant changes during the retinal remodeling at later stages of degeneration. This also suggests that the strategy of treating RP at later stages cannot assume intact RGCs.