Branch Retinal Artery Occlusions, Paracentral Acute Middle Maculopathy and Acute Macular Neuroretinopathy After COVID-19 Vaccinations.

Purpose: Potential retinal adverse events after COVID-19 vaccinations reported previously include paracentral acute middle maculopathy (PAMM), acute macular neuroretinopathy (AMN), and central serous chorioretinopathy. We report four cases of branch retinal artery occlusion (BRAO), one case of PAMM, and one case of AMN that occurred after administration of the Pfizer-BioNTech COVID-19 vaccine. Patients and Methods: We retrospectively reviewed the medical records of six patients who presented to Yame General Hospital or Oita University Hospital from July through October 2021. Results: Four patients (2 males) presented with visual field defects associated with BRAO, one male patient with PAMM, and one female patient with AMN after receiving the Pfizer-BioNTech COVID-19 vaccine. The mean age was 59.3 years; the mean best-corrected visual acuity was 20/21. The mean time from the last vaccination to the onset of visual field defect was 22.8 days. Five patients had received two doses of the vaccine and one patient one dose. Patients' medical history included diabetes mellitus in case 2, hypertension in cases 2, 3 and 6, and Alport syndrome and end-stage renal disease in case 6 for which the patient was undergoing regular hemodialysis. Conclusion: Although rare, retinal adverse events may occur after COVID-19 vaccinations. Further studies with a larger sample size should determine whether these retinal abnormalities are causally associated with COVID-19 vaccinations or just coincidental. Potential risks of BRAO/PAMM/AMN after COVID-19 vaccinations must be carefully weighed against the substantial benefit of COVID-19 vaccinations.

Exosc2 deficiency leads to developmental disorders by causing a nucleotide pool imbalance in zebrafish.

Exosc2 is one of the components of the exosome complex involved in RNA 3' end processing and degradation of various RNAs. Recently, EXOSC2 mutation has been reported in German families presenting short stature, hearing loss, retinitis pigmentosa, and premature aging. However, the in vivo function of EXOSC2 has been elusive. Herein, we generated Exosc2 knockout (exosc2-/-) zebrafish that showed larval lethality 13 days post fertilization, with microcephaly, loss of spinal motor neurons, myelin deficiency, and retinitis pigmentosa. Mechanistically, Exosc2 deficiency caused impaired mRNA turnover, resulting in a nucleotide pool imbalance. Rapamycin, which modulated mRNA turnover by inhibiting the mTOR pathway, improved nucleotide pool imbalance in exosc2-/- zebrafish, resulting in prolonged survival and partial rescue of neuronal defects. Taken together, our findings offer new insights into the disease pathogenesis caused by Exosc2 deficiency, and might help explain fundamental molecular mechanisms in neuronal diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and spinal muscular atrophy.

Tyrosine pre-transfer RNA fragments are linked to p53-dependent neuronal cell death via PKM2.

Fragments of transfer RNA (tRNA), derived either from pre-tRNA or mature tRNA, have been discovered to play an essential role in the pathogenesis of various disorders such as neurodegenerative disease. CLP1 is an RNA kinase involved in tRNA biogenesis, and mutations in its encoding gene are responsible for pontocerebellar hypoplasia type-10. Mutation of the CLP1 gene results in the accumulation of tRNA fragments of several different kinds. These tRNA fragments are expected to be associated with the disease pathogenesis. However, it is still unclear which of the tRNA fragments arising from the CLP1 gene mutation has the greatest impact on the onset of neuronal disease. We found that 5' tRNA fragments derived from tyrosine pre-tRNA (5' Tyr-tRF) caused p53-dependent neuronal cell death predominantly more than other types of tRNA fragment. We also showed that 5' Tyr-tRF bound directly to pyruvate kinase M2 (PKM2). Injection of zebrafish embryos with PKM2 mRNA ameliorated the neuronal defects induced in zebrafish embryos by 5' Tyr-tRF. Our findings partially uncovered a mechanistic link between 5' Tyr-tRF and neuronal cell death that is regulated by PKM2.