DNase I: A potential treatment for RVO
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Deoxyribonuclease I (DNase I), a well-established modulator of neutrophil extracellular traps (NETs), which are key players in vascular disease, might be protective for preventing and treating retinal vascular occlusion (RVO).1 First authors Guohua Deng, Xi Zou, and Zhinan Liu, from the Department of Ophthalmology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China, described their study.
The authors explained why NETs are candidates for analysis as a treatment for RVO.
NETs, they described, “are net-like, extracellular bactericidal structures released by NETosis in response to pathogenic stimuli. They are comprised of unwound DNA strands, histones, and bacteriostatic proteins2 and play a pivotal role in thrombosis pathogenesis, where their net-like structures provide a foundation for red blood cell and platelet aggregation, while their components activate the coagulation pathway.3”
The authors cited a study that found that inhibition of NETosis provided protection in cases of deep vein thrombosis.4 A recent study observed increased NETs-related markers in the peripheral blood of patients with RVO, which suggested an association between NETs and RVO development.5
Interestingly, while DNase I is described as “an economical, convenient, and widely used NETs inhibitor, it has rarely been used to prevent and treatment RVO.” In light of this, they sought to, first, verify if NETs are present in RVO and, second, assess the protective efficiency of DNase I in in vitro and in vivo experiments.
The authors analyzed circulating NETs biomarkers, i.e., cell-free DNA, myeloperoxidase DNA, and neutrophil elastase, in 30 patients with RVO and 30 healthy individuals. They also created an RVO mouse model using a retinal laser, and the mice were divided into the DNase I group and a control group. Tissue and blood samples were analyzed for NETs expression.
The investigators reported, “Our findings indicated an increase in circulating NETs biomarkers in human and mouse RVO cases and verified the presence of NETs in the retinal thrombus of the RVO model. Both in vitro and in vivo tests showed that DNase I attenuated NETs formation. Moreover, DNase I injections led to diminished NETs biomarker levels and a reduced duration of the thrombus after the RVO model was established.”
The investigators concluded, “The plasma NETs remnants were significantly increased in patients with RVO. In our animal experiments, upon successful establishment of the RVO model, NETs biomarkers showed a significant increase. With the injection of DNase I, NETs formation was inhibited, making the thrombus more unstable. This indicates a potential new target for RVO treatment. Further studies and clinical trials are necessary to identify the exact mechanism by which DNase I, in inhibiting NETs, may aid in the prevention and treatment of RVO.”
