Impact of preocular and ocular circulatory dynamics on the vascular density of retinal capillary plexuses and choriocapillaris.

PURPOSE: To highlight the influence of preocular and ocular vascular circulatory dynamics on the vascular density (VD) of retinal capillary plexuses (RCPs) and choriocapillaris (CC) in patients with and without cardiovascular risk (CVR) factors. METHODS: A retrospective observational study in patients with and without CVR factors (type 1 and 2 diabetes, arterial hypertension, and hypercholesterolemia). Fluorescein (FA) and indocyanine (ICGA) angiography circulatory times were arterial time (FAAT), start (FAstartLF) and end (FAendLF) of laminar flow, and arterial time (ICGAAT), respectively. OCT angiography VDs were superficial (VDSCP) and deep (VDDCP) RCPs and CC (VDCC) VDs. Correlation and regression analysis were performed after adjusting for confounding factors. RESULTS: 177 eyes of 177 patients (mean age: 65.2 ± 15.9 years, n = 92 with and 85 without CVR) were included. VDSCP and VDDCP were significantly inversely correlated with FAAT, FAstartLF and FAendLF likewise VDCC with ICGAAT. Correlations were stronger in patients without CVR than with CVR. CVR, FAAT, FAstartLF and FAendLF were more strongly correlated with VDDCP than VDSCP. FAAT, FAstartLF and FAendLF significantly impacted VDSCP and VDDCP, likewise ICGAAT impacted VDDCP. VDDCP was most strongly impacted by FAAT and FAstartLF. CONCLUSION: Ocular and pre-ocular circulatory dynamics significantly impacted RCPs and CC VDs, especially deep RCP.

Patient Perspective on the Monitoring of Their Wet Age-Related Macular Degeneration during Coronavirus Disease 2019: A Retrospective Study.

Background and Objectives: The purpose was to provide the patients' perspective on the monitoring of their wet age-related macular degeneration (wet AMD) during coronavirus disease 2019 (COVID-19) and the importance of telemedicine. Materials and Methods: Wet AMD patients that underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in two Swiss ophthalmology clinics, completed two questionnaires after the first confinement due to COVID-19 in Switzerland. The first evaluated their views concerning their adherence to scheduled injections during the confinement, and the application of telemedicine in the future. The second, adapted from the National Eye Institute Visual Function Questionnaire-25, assessed their opinions on visual function change during confinement. Results: From a total of 130 patients, 8.5% responded they did not respect their assigned schedule (group 1) while 91.5% responded they did (group 2). A total of 78.7% of group 2 considered treatment reception as more relevant compared to the risk of COVID-19 contraction. During the pre-lockdown period, group 2 patients required more help from others than group 1 patients (p = 0.02). In the possibility of another lockdown, 36.3% of group 1 and 8.7% of group 2 would choose telemedicine to monitor their wet AMD (p = 0.02), 54.5% and 86.9% would rather visit the clinic (p = 0.02), while 9.0% and 4.3% would cancel their appointment, respectively. It was found that 70% of group 1 and 33.6% of group 2 would prefer to use the telemedicine services than visiting a telemedicine centre (p = 0.04). Conclusions: During circumstances similar to the COVID-19 confinement, most patients would prefer to visit the clinic. Group 1 would prefer wet AMD monitoring via telemedicine at a higher rate than group 2.

The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.

Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.

Differential GAP requirement for Cdc42-GTP polarization during proliferation and sexual reproduction.

The formation of a local zone of Cdc42 GTPase activity, which governs cell polarization in many cell types, requires not only local activation but also switch-off mechanisms. In this study, we identify Rga3, a paralog of Rga4, as a novel Cdc42 GTPase-activating protein (GAP) in the fission yeast Schizosaccharomyces pombe Contrary to Rga4, Rga3 localizes with Cdc42-GTP to sites of polarity. Rga3 is dispensable for cell polarization during mitotic growth, but it limits the lifetime of unstable Cdc42-GTP patches that underlie cell pairing during sexual reproduction, masking a partly compensatory patch-wandering motion. In consequence, cells lacking rga3 hyperpolarize and lose out in mating competition. Rga3 synergizes with the Cdc42 GAPs Rga4 and Rga6 to restrict Cdc42-GTP zone sizes during mitotic growth. Surprisingly, triple-mutant cells, which are almost fully round, retain pheromone-dependent dynamic polarization of Cdc42-GTP, extend a polarized projection, and mate. Thus, the requirement for Cdc42-GTP hydrolysis by GAPs is distinct during polarization by intrinsic or extrinsic cues.