Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.
Objective To investigate the effect of the COVID-19 pandemic on the clinical presentation of acute, primary rhegmatogenous retinal detachment (RRD). Design Single-center, consecutive case series with historical controls. Subjects Consecutive patients presenting with primary RRD in a 50-day period during the USA COVID-19 pandemic (March 9 th - April 27 th , 2020) and the corresponding 50-day period in the previous year (March 4 th - April 22 th , 2019). Methods The cohorts were compared to assess demographic variables and clinical presentations. Multivariate logistic regression was used to identify factors predictive of presenting macular attachment status. Main Outcome Measure The primary outcome was the proportion of patients with macula-on RRD at presentation. Secondary outcomes included visual acuity (VA), duration of symptoms prior to presentation, proportion presenting within one day of symptom onset, and presence of primary proliferative vitreoretinopathy (PVR). Results Eighty-two patients were included in the 2020 cohort compared to 111 patients in the 2019 primary control cohort. Demographic factors were similar between the groups. Significantly fewer patients presented with macula-on RRD in the 2020 cohort (20/82 patients, 24.4%) than in 2019 (55/111 patients, 49.5%, p = 0.001). Patients in the 2020 cohort had worse median VA at presentation (LogMAR 1.00, Snellen 20/200 in 2020 versus LogMAR 0.48, Snellen 20/60 in 2019, p = 0.008), fewer patients presenting within one day of symptoms (16/80 patients [19.5%] in 2020 versus 41/106 patients [36.9%] in 2019, p = 0.005), and a greater proportion with primary PVR (11/82 patients [13.4%] in 2020 versus 5/111 patients [4.5%] in 2019, p = 0.03). In multivariate analysis, younger age (p = 0.03) and established patient status (p = 0.02) were independent predictors of macula-on status in the 2020 cohort. Conclusions Patients with primary RRD during the 2020 COVID-19 pandemic were less likely to be macula-on and more likely to have delayed presentation, worse vision, and PVR.
Purpose of review The purpose of this review is to describe the current clinical landscape of potential future therapies for both nonexudative (dry) and exudative (wet) age-related macular degeneration (AMD). We highlight some of the more promising treatments that are furthest along in development. Recent findings Patients with dry AMD have long been hoping for a highly efficacious treatment that may slow disease progression or even help regain vision. Patients with wet AMD have many effective treatment options but still there are those who have suboptimal responses or are burdened by the high frequency of treatment. We detail exciting new concepts and targets for novel medications. Specifically, for dry AMD we discuss research looking at complement inhibition, neuroprotection, visual cycle modulators, cell-based therapies, and anti-inflammatory agents. For wet AMD we summarize new, potentially more durable anti-vascular endothelial growth factor agents, extended release options, and gene therapy. Summary There are promising new strategies for AMD. Many of the potential new treatments are in or have recently completed phase 2 or phase 3 clinical trials with promising results thus far, including some that have received US Food and Drug Administration approval. Additional therapeutic breakthroughs will likely continue to occur thanks to the number of clinical trials that are nearing the finish line.
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