Host Immune Response and Associated Clinical Features in a Primary Cytomegalovirus Eye Infection Model Using Anterior Chamber Inoculation

Abstract

Purpose To investigate the pathogenesis of cytomegalovirus (CMV)-associated anterior segment infection in immunocompetent hosts and evaluate the effects of ganciclovir and glucocorticoid treatment in management of the disease. Methods We used an inoculation model to reproduce CMV anterior segment infection in immunocompetent rats. Flow cytometry, cytokine analysis, histopathological sections, and quantitative polymerase chain reaction were performed to investigate the immune response after CMV infection. The effects of ganciclovir and glucocorticoid treatment were also assessed. Results Anterior chamber inoculation of CMV in rats provoked characteristic pathological features of human CMV anterior segment infection. The innate and adaptive immunity sequentially developed in an anterior segment after inoculation, and the elevation of intraocular pressure (IOP) was highly associated with ocular infiltration and inflammation. Early ocular immune response reduced virus DNA in the anterior segment and alleviated viral lymphadenopathy. Early intervention with ganciclovir enhanced the release of cytokines associated with T response and facilitated recruitment of NKT and T cells in drainage lymph nodes. Glucocorticoid treatment, alone or combined with ganciclovir, decreased elevation of IOP but also impeded DNA clearance. Conclusions The inoculation model reproduced characteristic pathological features of human CMV anterior segment infection. The use of glucocorticoid in current practice may hinder viral clearance, and ganciclovir therapy can assist cytokine expression to combat the virus.

Technical Feasibility of Whole-eye Vascular Composite Allotransplantation: A Systematic Review

“…Common findings include the presence of macrophages, inflammatory cells, and signs of necrosis in transplanted retinal ganglion cells (RGCs) after graft loss. 14 , 19 , 40 – 42 Notably, one study found that perfusion of the postprocurement allograft with preservative solution before donor placement, and anastomosis resulted in decreased expression of phospho-c-Jun (PNJ+), an apoptotic marker. 43 In addition to histologic outcomes, the viability of ocular chambers was assessed, and intraocular pressures between the WET and native eye were found comparable.…”

“…Common findings include the presence of macrophages, inflammatory cells, and signs of necrosis in transplanted retinal ganglion cells (RGCs) after graft loss. 14,19,[40][41][42] Notably, one study found that perfusion of the postprocurement allograft PRS Global Open • 2023…”

“…Post-WET histological examination reported lymphocytic infiltration, corneal rejection, ocular tissue disorganization, and graft necrosis. 14,42 To mitigate such processes, our preliminary results indicate two main immunomodulators currently under investigation in the WET literature: tacrolimus 40 and cyclosporine A. 19 Tacrolimus remains a mainstay immunosuppressive in VCA and solid organ transplantation.…”