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Immunostaining of infected peripheral cornea for VACV antigen. Cells stained brown or red are positive for VACV. Nuclei were counterstained with hematoxylin. (A, B) Infected central and peripheral cornea, no primary antibody; (C, D) uninfected central and peripheral cornea; (E, F) infected central and peripheral cornea, eye with ocular disease, day 7. EP, corneal epithelium; S, stroma; EN, corneal endothelium; arrows, cells staining positive for viral antigen.
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Potentially blinding eye infections can occur after vaccination for Smallpox. Very little is known about the pathologic mechanisms that are involved and the information that is available was generated using rabbit models. The lack of immunological reagents for rabbits makes such studies difficult. We have characterized a mouse model of...
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... virus replication in corneal epithelium, stromal keratocytes, and infiltrating immune cells. To determine which cells in the cornea were infected, sections obtained from infected corneas on days 5 and 7 postinfection were stained with anti- VACV antibody (Fig. 6). Both central and peripheral corneas are shown. No staining was seen in the absence of the primary anti- body ( Fig. 6A and B). In uninfected corneas, we saw background staining for the corneal epithelium and endothelium, despite ex- tensive blocking and hydrogen peroxide pretreatment. In the presence of VACV antibody, there was more ...
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... epithelium, stromal keratocytes, and infiltrating immune cells. To determine which cells in the cornea were infected, sections obtained from infected corneas on days 5 and 7 postinfection were stained with anti- VACV antibody (Fig. 6). Both central and peripheral corneas are shown. No staining was seen in the absence of the primary anti- body ( Fig. 6A and B). In uninfected corneas, we saw background staining for the corneal epithelium and endothelium, despite ex- tensive blocking and hydrogen peroxide pretreatment. In the presence of VACV antibody, there was more intense staining of corneal epithelial cells, particularly near Bowman's layer, suggest- ing that replication was occurring in ...
Citations
... The co-culture induces Syk and Src phosphorylation to activate PI3K/Akt and Erk which lead to EMT and migration of HCECs keratitis [81] VACA 5 μl DMEM containing 1 × 10 7 VACA was applied to scraped cornea of female C57BL/6J mouse VACA induces the infiltration of neutrophils and lymphocytes in cornea stromal keratitis [115] SARS-CoV-2 ...
Following viral infection, the innate immune system senses viral products, such as viral nucleic acids, to activate innate defence pathways, leading to inflammation and apoptosis, control of cell proliferation, and consequently, threat to the whole body. The ocular surface is exposed to the external environment and extremely vulnerable to viral infection. Several studies have revealed that viral infection can induce inflammation of the ocular surface and reduce tear secretion of the lacrimal gland (LG), consequently triggering ocular morphological and functional changes and resulting in dry eye disease (DED). Understanding the mechanisms of DED caused by viral infection and its potential therapeutic strategies are crucial for clinical interventional advances in DED. This review summarizes the roles of viral infection in the pathogenesis of DED, applicable diagnostic and therapeutic strategies, and potential regions of future studies.
... The hypothermia and neutrophil mobilization observed in our study are not unique to ECM; they are also observed in certain, but not all, pathologies that utilize the C57BL/6 mouse. This includes models such as of viral infections [49][50][51][52][53][54], acute sepsis [55,56], and studies evaluating the toxicity of staphylococcal enterotoxin [57,58]. ...
Newly emerging data suggest that several neutrophil defense mechanisms may play a role in both aggravating and protecting against malaria. These exciting findings suggest that the balance of these cells in the host body may have an impact on the pathogenesis of malaria. To fully understand the role of neutrophils in severe forms of malaria, such as cerebral malaria (CM), it is critical to gain a comprehensive understanding of their behavior and functions. This study investigated the dynamics of neutrophil and T cell responses in C57BL/6 and BALB/c mice infected with Plasmodium berghei ANKA, murine models of experimental cerebral malaria (ECM) and non-cerebral experimental malaria, respectively. The results demonstrated an increase in neutrophil percentage and neutrophil-T cell ratios in the spleen and blood before the development of clinical signs of ECM, which is a phenomenon not observed in the non-susceptible model of cerebral malaria. Furthermore, despite the development of distinct forms of malaria in the two strains of infected animals, parasitemia levels showed equivalent increases throughout the infection period evaluated. These findings suggest that the neutrophil percentage and neutrophil-T cell ratios may be valuable predictive tools for assessing the dynamics and composition of immune responses involved in the determinism of ECM development, thus contributing to the advancing of our understanding of its pathogenesis.
... No ocular surface involvement was noted, and the patient was started on trifluridine 1% eye drops for prophylaxis and agreed to start HAART. During the next 2 weeks, despite treatment with oral tecovirimat (600 mg twice daily), HAART, and broad-spectrum antibiotics (intravenous daptomycin and levofloxacin), discrete lesions progressed to a necrotic rash of the face, expanding outward from initial foci and becoming confluent (figure 3A, days [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Qualitative PCR analysis of swabs from multiple skin sites consistently returned positive for non-variola Orthopoxvirus DNA (table), compatible with disseminated mpox. ...
... This auto inoculation most commonly causes a vesiculo pustular eyelid rash with blepharoconjunctivitis. 17 Vaccinia virus can also replicate successfully in the corneal epithelium and stromal keratocytes and, like variola virus, cause ulcerative keratitis and perforation. 17,18 Similar to its relatives, variola virus and vaccinia virus, monkeypox virus appears capable of locally inoculating and replicating within corneal tissue. In addition to more common presentations of mpoxrelated ophthalmic disease, providers should be aware of the potential for restrictive periorbital gangrene, corneal perforation, and globe compromise. ...
WHO has declared human mpox (formerly known as monkeypox) a global public health emergency since July, 2022. When case numbers were increasing, so did clinicians' exposures to new elements of the disease. Additionally, the burden of mpox is particularly apparent in immunocompromised patients, who can have more variable and severe manifestations of disease across organ systems. In this Grand Round, we report novel and severe oculocutaneous manifestations of mpox in this population, which are both sight and life threatening. Specifically, we highlight two patients with mpox and AIDS who had refractory skin necrosis that progressed to either ocular compromise or panfacial gangrene, or both. Both patients ultimately died due to systemic complications of their infections. Through clinical analogies, we show how past experiences with related orthopoxviruses, such as variola virus (smallpox) and vaccinia virus, can add useful context for understanding and treating these new disease states. We suspect that in patients who are immunocompromised, monkeypox virus can clinically evolve not only via viraemia but also through direct intradermal spread. We propose that intradermal spread occurs by a process clinically and immunologically analogous to progressive vaccinia, a complication previously seen after conventional smallpox vaccination. We share evidence in support of this theory and implications regarding early management and post-exposure prophylaxis for at-risk populations. Content note: this Grand Round contains graphic images of mpox lesions of the eyes and face.
