Background Pre-clinical testing of retinal pathology and treatment efficacy depends on reliable and valid measures of retinal function. The electroretinogram (ERG) and tests of visual acuity are the ideal standard, but can be unmeasurable while useful vision remains. Non-image-forming responses to light such as the pupillary light reflex (PLR) are attractive surrogates. However, it is not clear how accurately such responses reflect changes in visual capability in specific disease models. The purpose of this study was to test whether measures of non-visual responses to light correlate with previously determined visual function in two photoreceptor degenerations. Methods The sensitivity of masking behavior (light induced changes in running wheel activity) and the PLR were measured in 3-month-old wild-type mice (WT) with intact inner retinal circuitry, Pde6b-rd1/rd1 mice (rd1) with early and rapid loss of rods and cones, and Prph2-Rd2/Rd2 mice (Rd2) with a slower progressive loss of rods and cones. Results In rd1 mice, negative masking had increased sensitivity, positive masking was absent, and the sensitivity of the PLR was severely reduced. In Rd2 mice, positive masking identified useful vision at higher light levels, but there was a limited decrease in the irradiance sensitivity of negative masking and the PLR, and the amplitude of change for both underestimated the reduction in irradiance sensitivity of image-forming vision. Conclusions Together these data show that in a given disease, two responses to light can be affected in opposite ways, and that for a given response to light, the change in the response does not accurately represent the degree of pathology. However, the extent of the deficit in the PLR means that even a limited rescue of rod/cone function might be measured by increased PLR amplitude. In addition, positive masking has the potential to measure effective treatment in both models by restoring responses or shifting thresholds to lower irradiances.

BackgroundTriple negative breast cancer (TNBC) is aggressive and treatment resistant. Evidence suggests that deficits in melatonin signaling increase TNBC risk: conditions that suppress melatonin increased incidence, low melatonin receptor expression correlates with worse prognosis, and high-dose melatonin can inhibit TNBC. Together this suggests that normalizing pineal melatonin could reduce TNBC incidence and/or mortality. The goal of this study was to determine whether small physiological deficits in melatonin alone, can increase risk for TNBC, and how ‘normal’ melatonin would be protective.MethodsThe effect of melatonin treatment on 4t1 cellsin vitrowas measured using the MTT cell viability assay, and gene expression of breast cancer and melatonin signaling markers. The effect of pineal gland status on 4t1 cell allografts was tested in C3Sn mice (Mus Musculus) with either an intact pineal (control) or surgical removal of the pineal causing a ~50% deficit in plasma melatonin. Orthotopic tumors were assessed by histopathology and metastasis by strain specific qPCR against 4t1 cell and host gDNA.ResultsMelatonin treatment induced significant changes in gene expression, with a significant reduction in derived PAM50 Risk of Recurrence score (ROR in Not treated = 65.5 ± 10.6 Mean SEM; Treated with 25pg/ml of melatonin 20.8 ± 8.3; P = 0.008), suggesting melatonin treatment would improve prognosis. A ~50% reduction in plasma melatonin increased orthotopic tumors, but this was non-significant, and had no effect on metastasis from tail vein allograft.ConclusionsPhysiological deficits in melatonin do alter the oncogenic status of 4t1 tumor cells but this has only a limited effect on growth and metastasisin vivo. Lack of significance in orthotopic tumor formation may be due to small sample size, and it is possible that any protective effect of melatonin occurs earlier in tumor development than we have tested.