Progression of retinal choroidal neovascularization by latent human cytomegalovirus infection and immunological signaling among neonatal patients admitted to tertiary care hospital

Abstract

Choroidal neovascularization (CNV) is a serious condition that affects the retina, causing partial or complete blindness in people of different ages. While CNV is a common occurrence in various chorioretinopathies, research on its occurrence in neonates is limited. Human cytomegalovirus (HCMV) is a significant health threat to neonates, with a strong association with retinal angiogenesis. However, there has been limited investigation into HCMV‐associated CNV progression. In this article, we extensively studied the expression of different inflammatory cytokines and chemokines during latent HCMV‐associated retinal neovascularization. Our research found that HCMV‐induced CNV progression was significantly prominent in the presence of AT2R‐dependent angiogenesis (p < 0.001), whereas in the absence of HCMV, AT1R‐dependent CCL‐5‐mediated angiogenesis was documented. We also observed significant increases in CCL‐19, CCL‐21 chemokine responses, followed by CCR‐7 chemokine receptor activation (p < 0.001) in HCMV‐induced CNV patients compared to HCMV non‐induced CNV groups. Furthermore, significant changes in predictive chemokine markers of HCMV‐induced CNV were positively correlated with HCMV viremia. These immunological alterations ultimately lead to the switching of NFκB canonical and noncanonical pathways, respectively, in HCMV‐induced neonatal CNV and HCMV non‐induced CNV. This clinical observation presents a novel hypothesis that ocular HCMV latency poses a noteworthy risk factor for the progression of retinal neovascularization through a distinctive immunological signaling pathway. The current study represents the first of its kind to report on this association, which may have significant implications for the clinical management of patients with ocular HCMV.