Our eyes move constantly, even when we try to fixate our gaze. Fixational eye movements prevent and restore visual loss during fixation, yet the relative impact of each type of fixational eye movement remains controversial. For over five decades, the debate has focused on microsaccades, the fastest and largest fixational eye movements. Some recent studies have concluded that microsaccades counteract visual fading during fixation. Other studies have disputed this idea, contending that microsaccades play no significant role in vision. The disagreement stems from the lack of methods to determine the precise effects of microsaccades on vision versus those of other eye movements, as well as a lack of evidence that microsaccades are relevant to foveal vision. Here we developed a novel generalized method to determine the precise quantified contribution and efficacy of human microsaccades to restoring visibility compared with other eye movements. Our results indicate that microsaccades are the greatest eye movement contributor to the restoration of both foveal and peripheral vision during fixation. Our method to calculate the efficacy and contribution of microsaccades to perception can determine the strength of connection between any two physiological and/or perceptual events, providing a novel and powerful estimate of causal influence; thus, we anticipate wide-ranging applications in neuroscience and beyond.

Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor a (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive. The transactivation of ANXA2 promoter by PML/RARα fusion protein was 3.29 ± 0.13 fold higher than that by control pSG5 vector or wild-type RARα. The overexpression of ANXA2 in U937 transfected with full-length ANXA2 cDNA was associated with increased S100A10 subunit, although S100A10 transcripts remained constitutive. The tPA-dependent initial rate of plasmin generation (IRPG) in zinc-treated U937/PR9 increased by 2.13-fold, and cell invasiveness increased by 27.6%. Antibodies against ANXA2, S100A10, or combination of both all remarkably inhibited the IRPG and invasiveness in U937/PR9 and NB4. Treatment of zinc-induced U937/PR9 or circulating APL blasts with all-trans retinoic acid (ATRA) significantly reduced cell surface ANXA2 and S100A10 and associated reductions in IRPG and invasiveness. Thus, PML/RARα fusion protein transactivated the ANXA2 promoter to upregulate ANXA2 and accumulate S100A10. Increased AIIt promoted IRPG and invasiveness, both of which were partly abolished by antibodies against ANXA2 and S100A10 or by ATRA.

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Background Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has become first line therapy for diabetic macular edema. This study evaluated the efficacy and safety of intravitreal injection of Ranibizumab (IVR) as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy (PDR) patients with vitreous hemorrhage. Methods This pilot randomized controlled trial included 48 eyes with vitreous hemorrhage resulting from active PDR. Eyes were treated with IVR 1 or 3 days before vitrectomy or a sham subconjunctival injection 3 days before surgery. The occurrence of new tractional retinal detachment (TRD), total operation time, and intraoperative findings were compared. The concentrations of VEGF and connective tissue growth factor (CTGF) in aqueous humor and plasma collected at the time of IVR and vitrectomy were determined by ELISA. Results None of the patients who received IVR experienced new TRD. Ranibizumab injection improved intraoperative outcomes. The mean concentrations of VEGF in aqueous humor were significantly lower after than before IVR in patients who received IVR 1 and 3 days before surgery (P < 0.001 each). The CTGF/log10 (VEGF) ratio was significantly higher after than before IVR in patients who received IVR 3 days before vitrectomy (P = 0.046). Conclusion Preoperative IVR is an effective and safe strategy for the surgical treatment of severe PDR combined with vitreous hemorrhage. IVR 1 and 3 days before surgery can significantly reduce VEGF content in aqueous humor and effectively improve intraoperative conditions without causing TRD. Trial registration This study was registered with the Chinese Clinical Trial Registry. Name of the registry: Exploratory analysis of effect of intravitreal ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy. Trial registration number: ChiCTR-ONC-16009520. Date of registration: October 20, 2016. URL of trial registry record: http://www.chictr.org.cn/searchprojen.aspx