ABSTRACT
Diabetic retinopathy (DR) is an important ocular vascular disease in working-age adults. However, the molecular mechanism underlying retinal vascular dysfunction is still not fully understood in DR. Circular RNAs have been recognized as the crucial regulators in many biological processes and human diseases. Herein, we determined the role of circular RNA-MAP4K2 (cMAP4K2) in diabetes-induced retinal vascular dysfunction. The results showed that high glucose treatment led to increased levels of cMAP4K2 expression in vitro and in vivo. Silencing of cMAP4K2 could reduce endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviate retinal vascular dysfunction in vivo as shown by decreased vascular leakage and inflammation. By contrast, cMAP4K2 overexpression had an opposite effect on retinal vascular dysfunction. Mechanistically, cMAP4K2 acted as miR-377 sponge to affect the biological activity of miR-377, which led to increased expression of vascular endothelial growth factor A (VEGFA). Clinically, cMAP4K2 expression was significantly up-regulated in the clinical sample of DR patients. Collectively, cMAP4K2 is shown as a potential target for the diagnosis and treatment of diabetic retinopathy.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Germinal Center Kinases/metabolism , MicroRNAs , Cell Proliferation , Diabetes Mellitus/metabolism , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , Glucose/metabolism , Humans , MicroRNAs/metabolism , RNA, Circular/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: To describe cases of retinal vascular events shortly after administration of mRNA or adenoviral-vectored COVID-19 vaccines. DESIGN: Retrospective, multicenter case series. METHODS: Six cases of retinal vascular events shortly after receiving COVID-19 vaccines. RESULTS: A 38-year-old, otherwise healthy male patient presented with branch retinal arterial occlusion four days after receiving his second dose of SARS-CoV-2 vaccination with Comirnaty® (BioNTech®, Mainz, Germany; Pfizer®, New York City, NY, USA). An 81-year-old female patient developed visual symptoms twelve days after the second dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with a combined arterial and venous occlusion in her right eye. A 40-year-old male patient noticed blurry vision five days after his first dose of SARS-CoV-2 vaccination with Comirnaty® and was diagnosed with venous stasis retinopathy in his left eye. A 67-year-old male was diagnosed with non-arteritic anterior ischemic optic neuropathy in his right eye four days after receiving the first dose of Vaxzevria® (AstraZeneca®, Cambridge, UK). A 32-year-old man presented with a sudden onset of a scotoma two days after receiving the second dose of SARS-CoV-2 vaccination with Spikevax® (Moderna, Cambridge, UK) and was diagnosed with a circumscribed nerve fiber infarction. A 21-year-old female patient developed an acute bilateral acute macular neuroretinopathy three days after receiving the first dose of SARS-CoV2-vaccine Vaxzevria® (AstraZeneca®, Cambridge, UK). CONCLUSION: This case series describes six cases of retinal vascular events shortly after receiving mRNA or adenoviral-vectored COVID-19 vaccines. The short time span between received vaccination and occurrence of the observed retinal vascular events raises the question of a direct correlation. Our case series adds to further reports of possible side effects with potential serious post-immunization complications of COVID-19 vaccinations.
ABSTRACT
PURPOSE: To investigate the incidence of retinal vascular complications and risk factors in patients with chronic hepatitis C receiving interferon-ribavirin therapy in Taiwan. METHODS: By using the Taiwan National Health Insurance Research Database, we compared the incidence of retinal vascular complications between patients receiving and not receiving interferon-ribavirin treatment. The exposure and nonexposure groups were randomly 1:1 frequency-matched according to age, sex, income, urbanization level, hypertension, and diabetes. Incidence of each retinal vascular complication and hazard ratios were assessed in the follow-up evaluation. RESULTS: Of the sample of 4736 patients, a total of 182 patients (3.84%) developed retinopathy during the follow-up period, of which 110 patients (4.65%) received interferon-ribavirin therapy and 72 patients (3.04%) did not receive interferon-ribavirin therapy. After multivariate adjustments, the risk of retinopathy during the follow-up period was 1.533 (95% confidence interval [CI], 1.139-2.064; P = .0048) times higher in patients receiving interferon-ribavirin therapy than in those in the comparison cohort not receiving the therapy. Patients with hypertension compared with those without it (adjusted hazard ratio, 1.530; 95% CI, 1.069-2.135; P = .0125) also had an increased risk of retinopathy. CONCLUSIONS: Interferon-ribavirin therapy was associated with a 53.3% increased risk of retinal vascular complications compared with not receiving the therapy. Regular ophthalmologic examination is essential for patients receiving interferon-ribavirin, particularly those with hypertension.