Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis

Abstract

BackgroundDevelopment of congenital rubella syndrome associated with rubella virus infection during pregnancy is clinically important, but the pathogenicity of the virus remains unclear.MethodsPathological examination was conducted on 3 aborted fetuses with congenital rubella infection.FindingsAt autopsy, all 3 aborted fetuses showed congenital cataract confirmed by gross observation. Rubella virus infection occurred via systemic organs including circulating hematopoietic stem cells confirmed by immunohistochemical and molecular investigations, and major histopathogical changes were found in the liver. It is noteworthy that the virus infected the ciliary body of the eye, suggesting a possible cause of cataracts.InterpretationOur study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

Cataracts Pathophysiology and Managements

“…Roughly a third of pediatric cataracts are hereditary, one-third coexist with other ocular anomalies indicating a part of a multisystem syndrome, and another one-third have undetermined reasons. Pediatric causes of cataracts include [7] : Changes of the lens also frequently happen secondary to chronic uveitis, Fuchs' heterochromatic uveitis, and pseudo exfoliation syndrome [8,9] .…”

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

“…RuV infection of pregnant women has a pronounced teratogenic effect, especially during first gestational trimester (52). Pathological and immunohistochemical analyses of aborted fetuses with CRS demonstrated wide spread necrosis to organs including eye, heart, brain and ear, and are associated with the presence of rubella virus in all tissues (56). In-vitro studies suggest that RuV infection inhibits normal growth and differentiation of human embryonic mesenchymal cells (57).…”

“…Additionally, Rubella virus infection of placenta and embryonic cells induces interferon expression, especially in the placenta (60). The most commonly observed outcomes of CRS are congenital cataracts (97.4%), inner ear abnormalities (73.9%), microcephaly (68.4%), and congenital heart defects (57.9%) (45, 56, 61, 62). If the infection occurs during the first trimester, the rate of CRS is 80-90%.…”

The role of primary intraocular lens implantation in the risk of secondary glaucoma following congenital cataract surgery: A systematic review and meta-analysis

“…Congenital cataract is mainly caused by genetic or environmental factors, such as gene mutation or infection with rubella virus during early pregnancy [1]. It usually presents at birth and can be diagnosed by routine examination or is noticed in connection with leukocoria or strabismus.…”

“…At present, secondary glaucoma remains the most common complication threatening the vision after modern cataract surgery and may cause irreversible vision loss [8]. To provide evidence-based recommendations for healthcare professionals facing the same problems regarding the optimal therapeutic strategy and to provide a reference for the clinical practice, we conducted meta-analyses to evaluate the incidence of secondary glaucoma in (1) patients after primary IOL implantation, (2) patients with remaining aphakia, and (3) patients with secondary IOL implantation after cataract surgery.…”