Visual Function and Survival of Injured Retinal Ganglion Cells in Aged Rbfox1 Knockout Animals

Abstract

Rbfox1 is a multifunctional RNA binding protein that regulates various aspects of RNA metabolism important for neuronal differentiation and normal physiology. Rbfox1 has been associated with neurodevelopmental and neurological conditions as well as age-related neurodegenerative diseases such as Alzheimer’s and Parkinson’s. We have shown that in mammalian retinas Rbfox1 is expressed in retinal ganglion cells (RGCs) and in amacrine cells (ACs). This study investigates the effect of advanced age (22-month-old mice) on visual function, retinal morphology and survival of injured retinal ganglion cells (RGC) in Rbfox1 knockout (KO) animals. A visual cliff test, which was used to evaluate visual function, showed that 22-month old Rbfox1 KO mice have profound depth perception deficiency. Retinal gross morphology in these animals appeared to be normal. Optic nerve crush (ONC) induced axonal injury resulted in approximately 50% of RGC loss in both Rbfox1 KO and age-matched control animals: the average RGC densities in uninjured control and Rbfox1 KO animals were 6274 ± 1673 cells/mm2 and 6004 ± 1531 cells/mm2, respectively, whereas 1 week after ONC, RGC numbers in the retinas of control and Rbfox1 KO mice were reduced to 2998 ± 858 cells/mm2 and 3036 ± 857 cells/mm2, respectively (Rbfox1 KO vs. Rbfox1 KO + ONC, p < 0.0001 and control vs. control + ONC, p < 0.0001). No significant difference between RGC numbers in Rbfox1 KO + ONC and age-matched control + ONC animals was observed, suggesting that Rbfox1 has no effect on the survival of injured RGCs. Interestingly, however, contrary to a commonly accepted view that the number of RGCs in old (18 month of age) compared to young animals is reduced by approximately 40%, the RGC densities in 22-month-old mice in this study were similar to those of 4-month-old counterparts.