The effect of Rbfox2 modulation on retinal transcriptome and visual function

Rbfox proteins regulate alternative splicing, mRNA stability and translation. These proteins are involved in neurogenesis and have been associated with various neurological conditions. Here, we analyzed Rbfox2 expression in adult and developing mouse retinas and the effect of its downregulation on visual function and retinal transcriptome. In adult rodents, Rbfox2 is expressed in all retinal ganglion cell (RGC) subtypes, horizontal cells, as well as GABAergic amacrine cells (ACs). Among GABAergic AC subtypes, Rbfox2 was colocalized with cholinergic starburst ACs, NPY (neuropeptide Y)- and EBF1 (early B-cell factor 1)-positive ACs. In differentiating retinal cells, Rbfox2 expression was observed as early as E12 and, unlike Rbfox1, which changes its subcellular localization from cytoplasmic to predominantly nuclear at around P0, Rbfox2 remains nuclear throughout retinal development. Rbfox2 knockout in adult animals had no detectable effect on retinal gross morphology. However, the visual cliff test revealed a significant abnormality in the depth perception of Rbfox2-deficient animals. Gene set enrichment analysis identified genes regulating the RNA metabolic process as a top enriched class of genes in Rbfox2-deficient retinas. Pathway analysis of the top 100 differentially expressed genes has identified Rbfox2-regulated genes associated with circadian rhythm and entrainment, glutamatergic/cholinergic/dopaminergic synaptic function, calcium and PI3K-AKT signaling.

Evaluation of visual function in Royal College of Surgeon rats using a depth perception visual cliff test

Preserving of vision is the main goal in vision research. The presented research evaluates the preservation of visual function in Royal College of Surgeon (RCS) rats using a depth perception test. Rats were placed on a stage with one side containing an illusory steep drop (“cliff”) and another side with a minimal drop (“table”). Latency of stage dismounting and the percentage of rats that set their first foot on the “cliff” side were determined. Nondystrophic Long–Evans (LE) rats were tested as control. Electroretinogram and histology analysis were used to determine retinal function and structure. Four-week-old RCS rats presented a significantly shorter mean latency to dismount the stage compared with 6-week-old rats (mean ± standard error, 13.7 ± 1.68 vs. 20.85 ± 6.5 s, P = 0.018). Longer latencies were recorded as rats aged, reaching 45.72 s in 15-week-old rats (P < 0.00001 compared with 4-week-old rats). All rats at the age of 4 weeks placed their first foot on the table side. By contrast, at the age of 8 weeks, 28.6% rats dismounted on the cliff side and at the age of 10 and 15 weeks, rats randomly dismounted the stage to either table or cliff side. LE rats dismounted the stage faster than 4-week-old RCS rats, but the difference was not statistically significant (7 ± 1.58 s, P = 0.057) and all LE rats dismounted on the table side. The latency to dismount the stage in RCS rats correlated with maximal electroretinogram b-wave under dark and light adaptation (Spearman’s rho test = −0.603 and −0.534, respectively, all P < 0.0001), outer nuclear layer thickness (Spearman’s rho test = −0.764, P = 0.002), and number of S- and M-cones (Spearman’s rho test = −0.763 [P = 0.002], and −0.733 [P = 0.004], respectively). The cliff avoidance test is an objective, quick, and readily available method for the determination of RCS rats’ visual function.

Availability of Peripheral Optic Flow Influences Whether Infants Cross a Visual Cliff

This report describes a novel test of the prediction that locomotion-induced changes in an infant’s functional utilization of peripheral lamellar optic flow (PLOF) for postural stability contributes to avoidance of the deep side of a visual cliff. To test the prediction, a corridor, with either low-textured or high-textured walls, was constructed to run the length of a visual cliff. The infants, 9.5-month-olds with varying amounts of hands-and-knees crawling experience, were randomly assigned to the low-texture (n = 30) or the high-texture condition (n = 32). Consistent with predictions, the findings revealed significant interactions between crawling experience and texture condition for the probability of crossing and the latency to venture onto the deep side of the cliff. Most notably, more experienced crawlers, but not less experienced crawlers, were significantly more likely to cross the visual cliff to the parents and ventured onto the cliff faster in the high-texture condition than in the low-texture condition. The availability of PLOF thus had an effect on infants’ crossing behavior on the visual cliff. We interpret these findings as evidence for a three-step process in which locomotor-induced changes in visual proprioception play a central role in the development of wariness of heights.