Small Noncoding RNA (sncRNA1) within the Latency-Associated Transcript Modulates Herpes Simplex Virus 1 Virulence and the Host Immune Response during Acute but Not Latent Infection.

The HSV-1 latency-associated transcript (LAT) locus contains two small noncoding RNA (sncRNA) sequences (sncRNA1 and sncRNA2) that are not microRNAs (miRNAs). We recently reported that sncRNA1 is more important for in vitro activation of the herpesvirus entry mediator than sncRNA2, but its in vivo function is not known. To determine the role, if any, of sncRNA1 during herpes simplex virus 1 (HSV-1) infection in vivo, we deleted the 62-bp sncRNA1 sequence in HSV-1 strain McKrae using dLAT2903 (LAT-minus) virus, creating ΔsncRNA1 recombinant virus. Deletion of the sncRNA1 in ΔsncRNA1 virus was confirmed by complete sequencing of ΔsncRNA1 virus and its parental virus (i.e., McKrae). Replication of ΔsncRNA1 virus in tissue culture or in the eyes of infected mice was similar to that of HSV-1 strain McKrae and dLAT2903 viruses. However, the absence of sncRNA1 significantly reduced the levels of ICP0, ICP4, and gB but not LAT transcripts in infected rabbit skin cells in vitro. In contrast, the absence of sncRNA1 did reduce LAT expression in trigeminal ganglia (TG), but not in corneas, by day 5 postinfection (p.i.) in infected mice. Levels of eye disease in mice infected with ΔsncRNA1 or McKrae virus were similar, and despite reduced LAT levels in TG during acute ΔsncRNA1 infection, McKrae and ΔsncRNA1 viruses did not affect latency or reactivation on day 28 p.i. However, mice infected with ΔsncRNA1 virus were more susceptible to ocular infection than their wild-type (WT) counterparts. Expression of host immune response genes in corneas and TG of infected mice during primary infection showed reduced expression of beta interferon (IFNß) and IFNγ and altered activation of key innate immune pathways, such as the JAK-STAT pathway in ΔsncRNA1 virus compared with parental WT virus. Our results reveal novel functions for sncRNA1 in upregulating the host immune response and suggest that sncRNA1 has a protective role during primary ocular HSV-1 infection. IMPORTANCE HSV-1 latency-associated transcript (LAT) plays a major role in establishing latency and reactivation; however, the mechanism by which LAT controls these processes is largely unknown. In this study, we sought to establish the role of the small noncoding RNA1 (sncRNA1) encoded within LAT during HSV-1 ocular infection. Our results suggest that sncRNA1 has a protective role during acute ocular infection by modulating the innate immune response to infection.

SARS-CoV-2 and the Eye: The Pandora's Box of Ocular Immunology.

The Pandora's box myth addresses the evilness in the world that undisputedly nowadays is identified in severe acute respiratory syndrome (SARS)-Coronavirus 2 (CoV-2), formerly known as Covid-19, which belongs to coronaviridae family, identified in Wuhan, Hubei district of the Republic of China in December 2019. Since then, SARS-CoV-2 has affected ∼180 million people and made almost 4 million victims, with a mortality rate of 6.1%, which is 6 times higher than influenza virus. However, coronaviruses are well known in the ophthalmology field because they were used in the so-called experimental coronavirus retinopathy model. That model certainly brings intriguing concepts for understanding coronavirus pathophysiology, which may have important implications on treatment strategies. Certainly, the recent availability of vaccines gives hope on the control of virus spreading; however, vaccines might create immune reactions involving the eye structure. In this study, we reviewed the literature and elaborated the available data to speculate on possible new interpretation of both pathophysiology and treatment of SARS-CoV-2.

The Epithelial Cell Glycocalyx in Ocular Surface Infection.

The glycocalyx is the main component of the transcellular barrier located at the interface between the ocular surface epithelia and the external environment. This barrier extends up to 500 nm from the plasma membrane and projects into the tear fluid bathing the surface of the eye. Under homeostatic conditions, defense molecules in the glycocalyx, such as transmembrane mucins, resist infection. However, many pathogenic microorganisms have evolved to exploit components of the glycocalyx in order to gain access to epithelial cells and consequently exert deleterious effects. This manuscript reviews the implications of the ocular surface epithelial glycocalyx to bacterial, viral, fungal and parasitic infection. Moreover, it presents some ongoing controversies surrounding the functional relevance of the epithelial glycocalyx to ocular infectious disease.

The cornea IV immunology, infection, neovascularization, and surgery chapter 1: Corneal immunology.

PURPOSE: of Review: This review offers an informed and up-to-date insight on the immune profile of the cornea and the factors that govern the regulation of such a unique immune environment. SUMMARY: The cornea is a unique tissue that performs the specialized task of allowing light to penetrate for visual interpretation. To accomplish this, the ocular surface requires a distinct immune environment that is achieved through unique structural, cellular and molecular factors. Not only must the cornea be able to fend off invasive infectious agents but also control the inflammatory response as to avoid collateral, and potentially blinding damage; particularly of post-mitotic cells such as the corneal endothelium. To combat infections, both innate and adaptive arms of the inflammatory immune response are at play in the cornea. Dendritic cells play a critical role in coordinating both these responses in order to fend off infections. On the other side of the spectrum, the ocular surface is also endowed with a variety of anatomic and physiologic components that aid in regulating the immune response to prevent excessive, potentially damaging, inflammation. This attenuation of the immune response is termed immune privilege. The balance between pro and anti-inflammatory reactions is key for preservation of the functional integrity of the cornea. RECENT FINDINGS: The understanding of the molecular and cellular factors governing corneal immunology and its response to antigens is a growing field. Dendritic cells in the normal cornea play a crucial role in combating infections and coordinating the inflammatory arms of the immune response, particularly through coordination with T-helper cells. The role of neuropeptides is recently becoming more highlighted with different factors working on both sides of the inflammatory balance.

Absence of Signal Peptide Peptidase, an Essential Herpes Simplex Virus 1 Glycoprotein K Binding Partner, Reduces Virus Infectivity In Vivo.

We previously reported that herpes simplex virus (HSV) glycoprotein K (gK) binds to signal peptide peptidase (SPP), also known as minor histocompatibility antigen H13. Binding of gK to SPP is required for HSV-1 infectivity in vitro SPP is a member of the γ-secretase family, and mice lacking SPP are embryonic lethal. To determine how SPP affects HSV-1 infectivity in vivo, the SPP gene was deleted using a tamoxifen-inducible Cre recombinase driven by the ubiquitously expressed ROSA26 promoter. SPP mRNA was reduced by more than 93% in the cornea and trigeminal ganglia (TG) and by 99% in the liver of tamoxifen-injected mice, while SPP protein expression was reduced by 90% compared to the level in control mice. Mice lacking SPP had significantly less HSV-1 replication in the eye as well as reduced gK, UL20, ICP0, and gB transcripts in the cornea and TG compared to levels in control mice. In addition, reduced infiltration of CD45+, CD4+, CD8+, F4/80+, CD11c+, and NK1.1+ T cells was observed in the cornea and TG of SPP-inducible knockout mice compared to that in control mice. Finally, in the absence of SPP, latency was significantly reduced in SPP-inducible knockout mice compared to that in control mice. Thus, in this study we have generated SPP-inducible knockout mice and shown that the absence of SPP affects virus replication in the eye of ocularly infected mice and that this reduction is correlated with the interaction of gK and SPP. These results suggest that blocking this interaction may have therapeutic potential in treating HSV-1-associated eye disease.IMPORTANCE Glycoprotein K (gK) is an essential and highly conserved HSV-1 protein. Previously, we reported that gK binds to SPP, an endoplasmic reticulum (ER) protein, and blocking this binding reduces virus infectivity in vitro and also affects gK and UL20 subcellular localization. To evaluate the function of gK binding to SPP in vivo, we generated SPP-inducible knockout mice and observed the following in the absence of SPP: (i) that significantly less HSV-1 replication was seen in ocularly infected mice than in control mice; (ii) that expression of various HSV-1 genes and cellular infiltrates in the eye and trigeminal ganglia of infected mice was less than that in control mice; and (iii) that latency was significantly reduced in infected mice. Thus, blocking of gK binding to SPP may be a useful tool to control HSV-1-induced eye disease in patients with herpes stromal keratitis (HSK).

Immune checkpoint inhibitors: what neuro-ophthalmologists need to know.

PURPOSE OF REVIEW: Immune checkpoint inhibitors are currently an exceedingly powerful tool in the management of hitherto incurable malignancies and their use in clinical practice is expected to increase in the near future. The purpose of this review is to discuss the current medical uses of checkpoint inhibitors with a focus on their neuro-ophthalmic side-effects. RECENT FINDINGS: Immune checkpoint inhibitors have emerged as a promising breakthrough in the treatment of several tumor types. However, these targeted therapies can induce a wide range of immune-related ophthalmic and neuro-ophthalmic toxicities. It is important for neuro-ophthamologists to promptly recognize and manage these adverse events that can potentially threaten vision. SUMMARY: There are currently seven FDA-approved immune checkpoint inhibitors and several ones are under investigation. In general, immunotherapy is considered a well tolerated, safe and efficacious treatment option for many cancer patients. Nevertheless, because of their unique mechanism of action, these molecules can alter the immune response and result in immune-related adverse effects in almost every organ with an estimated incidence of ophthalmic side effects in this patient population of less than 1%.

TIPE2 Suppresses Pseudomonas aeruginosa Keratitis by Inhibiting NF-κB Signaling and the Infiltration of Inflammatory Cells.

BACKGROUND: The role of tumor necrosis factor α (TNF-α) induced protein 8-like-2 (TIPE2) in Pseudomonas aeruginosa (PA) keratitis was explored. METHODS: Eight-week-old TIPE2 knockout (TIPE2-/-) C57BL/6 mice and their wild-type (WT) littermates were used. Corneal disease was graded at 1, 2, and 3 days postinfection, and slit lamp, clinical score, histopathology, and immunostaining were performed in the infected corneas. The corneas were harvested, and messenger ribonucleic acid (mRNA) levels of TNF-α, interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were tested. Enzyme-linked immunosorbent assay (ELISA) determined the protein levels, and nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling molecules were tested by Western blot. In vitro human corneal epithelial cells (HCECs) were used to determine the relationship between TIPE2 and TAK1. The HCECs were treated with TIPE2 short hairpin ribonucleic acid (shRNA) and lipopolysaccharide (LPS) to test the NF-κB signaling molecules by Western blot. RESULTS: Pseudomonas aeruginosa infection induced a decreased expression of TIPE2 in mouse corneas 2 days postinfection. Compared with the control group, TIPE2-deficient mice were susceptible to infection with PA and showed increased corneal inflammation. Reduced NF-κB signaling and inflammatory cell infiltration were required in the TIPE2-mediated immune modulation. CONCLUSIONS: TIPE2 promoted host resistance to PA infection by suppressing corneal inflammation via regulating TAK1 signaling negatively and inhibiting the infiltration of inflammatory cells.

Uveitis causes according to immune status of patients.

PURPOSE: The advances in medicine have led to an increased number of people living with some form of immunodeficiency. Most ocular infections in immunocompromised patients may lead to irreversible blindness. We identify the causes of uveitis in immunocompetent and immunocompromised patients. METHODS: A retrospective cohort study of 1354 consecutive patients. All patients underwent a standard work-up for uveitis. RESULTS: An immunocompromised state was identified in 171/1354 patients (13%), of whom 40 had Human immunodeficiency virus (HIV) infection, 52 received immunosuppressive medications, 28 had concurrent malignant disorder and 20 had other causes for their immunosuppression. In addition, 93/1354 patients (7%) had diabetes mellitus (DM). The prevalence of intraocular infections was much higher in immunocompromised patients than in immunocompetent patients and DM (p < 0.001). Causes of uveitis differed between the diverse immunocompromised groups. The non-HIV immunocompromised patients showed primarily intraocular herpes simplex and varicella zoster virus infections, whilst HIV-positive patients exhibited frequently cytomegalovirus (CMV) retinitis and syphilis. Patients with generalized malignancies were characterized by a lower prevalence of infections and higher prevalence of sarcoidosis. Patients with DM typically showed sarcoidosis and bacterial intraocular infections. The percentage of undetermined uveitis diagnoses was markedly lower in immunosuppressed patients (p < 0.001). CONCLUSION: In immunocompromised patients with uveitis, infections were diagnosed in 46% of cases in contrast to 12% in the immunocompetent patients. The causes of uveitis differed among the various types of immunosuppression. Immunocompromised patients with uveitis require a rapid assessment for the most expected infections.

Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier.

Despite flaviviruses remaining the leading cause of systemic human infections worldwide, ocular manifestations of these mosquito-transmitted viruses are considered relatively uncommon in part due to under-reporting. However, recent outbreaks of Zika virus (ZIKV) implicated in causing multiple ocular abnormalities, such as conjunctivitis, retinal hemorrhages, chorioretinal atrophy, posterior uveitis, optic neuritis, and maculopathies, has rejuvenated a significant interest in understanding the pathogenesis of flaviviruses, including ZIKV, in the eye. In this review, first, we summarize the current knowledge of the major flaviviruses (Dengue, West Nile, Yellow Fever, and Japanese Encephalitis) reported to cause ocular manifestations in humans with emphasis on recent ZIKV outbreaks. Second, being an immune privilege organ, the eye is protected from systemic infections by the presence of blood-retinal barriers (BRB). Hence, we discuss how flaviviruses modulate retinal innate response and breach the protective BRB to cause ocular or retinal pathology. Finally, we describe recently identified infection signatures of ZIKV and discuss whether these system biology-predicted genes or signaling pathways (e.g., cellular metabolism) could contribute to the pathogenesis of ocular manifestations and assist in the development of ocular antiviral therapies against ZIKV and other flaviviruses.

The pathogenic role of dendritic cells in non-infectious anterior uveitis.

BACKGROUND: Anterior uveitis (AU) is characterised by infiltration of immune cells into the anterior chamber of the eye. Dendritic cells (DC) are professional antigen presenting cells that initiate and promote inflammation. This study aims to characterise DC in AU and to examine the effects of aqueous humor (AqH) on DC maturation and function. METHODS: The frequency and phenotype of AU and healthy control (HC) circulating DC was examined. AU and HC AqH was immunostained and assessed by flow cytometry. The effect of AU and HC AqH on DC activation and maturation was examined and subsequent effects on CD4+ T cell proliferation assessed. RESULTS: AU peripheral blood demonstrated decreased circulating myeloid and plasmacytoid DC. Within AU AqH, three populations of CD45+ cells were significantly enriched compared to HC; DCs (CD11c+ HLA-DR+), neutrophils (CD15+ CD11c+) and T cells (CD4+ and CD8+). A significant increase in IFNγ, IL8 and IL6 was observed in the AU AqH, which was also significantly higher than that of paired serum. AU AqH induced expression of CD40 and CD80 on DC, which resulted in increased T cell proliferation and the production of GM-CSF, IFNγ and TNFα. CONCLUSION: DC are enriched at the site of inflammation in AU. Our data demonstrate an increase in inflammatory mediators in the AU inflamed microenvironment. AU AqH can activate DC, leading to subsequent proliferation and activation of effector T cells. Thus, the AU microenvironment contributes to immune cell responses and intraocular inflammation.

STAT-3-independent production of IL-17 by mouse innate-like αß T cells controls ocular infection.

Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4+ T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αß+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3. In our current study, we identify promyelocytic leukemia zinc finger (PLZF)-expressing iNKT, CD4-/CD8+, and CD4-/CD8- (DN) αß+T cells, which produce IL-17 in response to TCR and IL-1 receptor ligation independently of STAT-3 signaling. Notably, this noncanonical pathway of IL-17 production may be important in mucosal defense and is by itself sufficient to control pathogenic Staphylococcus aureus infection at the ocular surface.

An M2 Rather than a TH2 Response Contributes to Better Protection against Latency Reactivation following Ocular Infection of Naive Mice with a Recombinant Herpes Simplex Virus 1 Expressing Murine Interleukin-4.

We found previously that altering macrophage polarization toward M2 responses by injection of colony-stimulating factor 1 (CSF-1) was more effective in reducing both primary and latent infections in mice ocularly infected with herpes simplex virus 1 (HSV-1) than M1 polarization by gamma interferon (IFN-γ) injection. Cytokines can coordinately regulate macrophage and T helper (TH) responses, with interleukin-4 (IL-4) inducing type 2 TH (TH2) as well as M2 responses and IFN-γ inducing TH1 as well as M1 responses. We have now differentiated the contributions of these immune compartments to protection against latency reactivation and corneal scarring by comparing the effects of infection with recombinant HSV-1 in which the latency-associated transcript (LAT) gene was replaced with either the IL-4 (HSV-IL-4) or IFN-γ (HSV-IFN-γ) gene using infection with the parental (LAT-negative) virus as a control. Analysis of peritoneal macrophages in vitro established that the replacement of LAT with the IL-4 or IFN-γ gene did not affect virus infectivity and promoted polarization appropriately. Protection against corneal scarring was significantly higher in mice ocularly infected with HSV-IL-4 than in those infected with HSV-IFN-γ or parental virus. Levels of primary virus replication in the eyes and trigeminal ganglia (TG) were similar in the three groups of mice, but the numbers of gC+ cells were lower on day 5 postinfection in the eyes of HSV-IL-4-infected mice than in those infected with HSV-IFN-γ or parental virus. Latency and explant reactivation were lower in both HSV-IL-4- and HSV-IFN-γ-infected mice than in those infected with parental virus, with the lowest level of latency being associated with HSV-IL-4 infection. Higher latency correlated with higher levels of CD8, PD-1, and IFN-γ mRNA, while reduced latency and T-cell exhaustion correlated with lower gC+ expression in the TG. Depletion of macrophages increased the levels of latency in all ocularly infected mice compared with their undepleted counterparts, with macrophage depletion increasing latency in the HSV-IL-4 group greater than 3,000-fold. Our results suggest that shifting the innate macrophage immune responses toward M2, rather than M1, responses in HSV-1 infection would improve protection against establishment of latency, reactivation, and eye disease.IMPORTANCE Ocular HSV-1 infections are among the most frequent serious viral eye infections in the United States and a major cause of virus-induced blindness. As establishment of a latent infection in the trigeminal ganglia results in recurrent infection and is associated with corneal scarring, prevention of latency reactivation is a major therapeutic goal. It is well established that absence of latency-associated transcripts (LATs) reduces latency reactivation. Here we demonstrate that recombinant HSV-1 expressing IL-4 (an inducer of TH2/M2 responses) or IFN-γ (an inducer of TH1/M1 responses) in place of LAT further reduced latency, with HSV-IL-4 showing the highest overall protective efficacy. In naive mice, this higher protective efficacy was mediated by innate rather than adaptive immune responses. Although both M1 and M2 macrophage responses were protective, shifting macrophages toward an M2 response through expression of IL-4 was more effective in curtailing ocular HSV-1 latency reactivation.

An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells.

Mucosal sites such as the intestine, oral cavity, nasopharynx, and vagina all have associated commensal flora. The surface of the eye is also a mucosal site, but proof of a living, resident ocular microbiome remains elusive. Here, we used a mouse model of ocular surface disease to reveal that commensals were present in the ocular mucosa and had functional immunological consequences. We isolated one such candidate commensal, Corynebacterium mastitidis, and showed that this organism elicited a commensal-specific interleukin-17 response from γδ T cells in the ocular mucosa that was central to local immunity. The commensal-specific response drove neutrophil recruitment and the release of antimicrobials into the tears and protected the eye from pathogenic Candida albicans or Pseudomonas aeruginosa infection. Our findings provide direct evidence that a resident commensal microbiome exists on the ocular surface and identify the cellular mechanisms underlying its effects on ocular immune homeostasis and host defense.

Human antimicrobial peptides in ocular surface defense.

Sight depends on the passage of light through the transparent cornea and being focused on the fovea. Its exposed position renders it vulnerable to microbial infection. The cornea has developed a wide array of defense mechanisms against infection, of which endogenous antimicrobial peptides (AMPs) are key. AMPs are essentially small molecular weight cationic peptides with a wide range of activity against virus, bacteria, fungi and parasites. Some proteins such as RNases and S100As are also included in this group. Several AMPs act synergistically allowing low expression of multiple AMPs to act efficiently. AMPs also have a range of non-microbicidal functions and serve as signaling molecules, immunomodulators; show anti-tumour activity, and influence vascularization and wound healing. Different toll-like receptors (TLR) have been implicated in the preferential induction of specific AMPs. A range of bacteria, including mycobacteria tuberculosis, viruses including herpes virus, fungi and parasites including acanthamoeba, that cause ocular infections have been shown to induce specific AMPs via TLR activation. Non-TLR mediated induction of AMP expression can occur and several molecules such as L-isoleucine, sodium butyrate, vitamin D3, phenylbutyrate, vasoactive intestinal peptide, and etinostat have been identified in this regard. Given the rising microbe resistance to antibiotics, the slow rate of development of new antibiotics and the limited access to effective antibiotics by patients living in the developing world, an ideal solution would be to find AMPs that are effective singly or in combination with each other or other antimicrobial proteins to reduce, if possible eliminate reliance on antibiotics alone.

Herpes simplex virus-1 infects the olfactory bulb shortly following ocular infection and exhibits a long-term inflammatory profile in the form of effector and HSV-1-specific T cells.

BACKGROUND: Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency. METHODS: Scarified corneas of C57BL/6 or reporter-inducible Rosa mice (RosaTd/Tm) were inoculated with HSV-1 and assessed for viral dissemination into the peripheral nervous system (PNS) and CNS by RT-PCR and confocal microscopy. T cells and the resident microglia activation signatures were analyzed by flow cytometry. T cell effector function in the form of IFN-γ secretion was measured by T cells isolated from OB in comparison to T cells from other nervous system sites known to harbor HSV-1-specific memory T cells. RESULTS: Following ocular infection, HSV-1 viral titers from nasal secretions were detected as early as 48 h through 8 days post infection (8 DPI). HSV-1 gene expression was expressed as early as 2 days following ocular infection in the OB and was consistent with an enhanced expression in the ophthalmic, maxillary, and mandibular branch of the trigeminal nerve ganglia (TG). Rosa fluorescence protein expression (RFP+) representing HSV-1-infected cells from RosaTd/Tm mice was detected in the OB before other areas of the CNS (2 DPI). Additionally, during acute infection, most infected cells appeared to be anatomically distributed within the OB rather than other regions of the CNS. During latency (i.e., 30 DPI and beyond) despite no detectable infectious virus or lytic gene expression and low levels of latency associated transcripts, total effector (CD44+ CD62-) CD4+ T, CD8+ T, HSV-1-specific CD8+ T cells, and MHC class II positive resident microglia numbers continued to increase. CD4+ and CD8+ T cell populations isolated from the OB during latency were capable of responding to PMA/ionomycin in the production of IFN-γ similar to T cells from other tissue that possess latent virus including the TG and brain stem. CONCLUSIONS: It is currently understood that HSV-1 traffics to the TG following ocular infection. We have identified a second conduit by which HSV-1 can directly access the CNS bypassing the brain stem. We have also recognized that the OB is unique in that during HSV-1 latency, latency-associated transcripts levels were marginally above uninfected controls. Despite these findings, the local immune response mimicked the phenotype of an active infection during latency.

[Contact lens care and maintenance]. / Surveillance, hygiène et entretien des lentilles de contact.

All contact lenses with replacement schedules longer than daily must be maintained. At each step of their use, the lenses may be contaminated. Contact lens solutions perform the essential functions of cleaning, decontaminating and preserving the lenses to prevent infectious problems and improve wearing comfort. Contact lens contamination essentially comes from hands, cleaning solutions, cases, water and the environment. The pathogenic microorganisms are mainly Gram-negative bacteria, fungi and amoebae. Contact lens deposits may or may not have an organic origin. Their presence increases the risk of infection because they serve as a nutrient matrix for microbes, and they are responsible for wearing discomfort. Contact lens solutions differ in their composition, their mechanism of action and the concentration of the various agents. To prescribe the best lens care system to each wearer and for each material, it is necessary to be very familiar with them. Maintenance is the main cause of discomfort with contact lenses, either through improper use, solution-material incompatibility, or a reaction of the wearer to the components.

A Mouse Model for Ocular Surface Staphylococcus aureus Infection.

Creation of an appropriate animal model that accurately reflects the disease and host immune response to bacterial infection in humans is a major challenge in ocular-surface infection research. For decades, mice have been the ideal small animal model for ocular-surface infection research because of the availability and relatively low cost of various genetic backgrounds, targeted defects, and immunologic reagents. By employing different combinations of mouse and bacterial strains, murine infection models can be used to explore a complete picture of bacterial infection and innate immunity of the ocular surface. A murine model of Staphylococcus aureus infection under normal ocular circumstances is presented here as a convenient and tractable model system in which to study mammalian host responses to pathogens. © 2017 by John Wiley & Sons, Inc.

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Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence.

Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence.

Infectious dose and repeated infections are key factors influencing immune response characteristics in guinea pig ocular chlamydial infection.

The aim of this study was to determine whether infectious dose of Chlamydia caviae after repeated infections influences the immunological responses and subsequent clearance of pathogen at the ocular surface of guinea pigs. Animals were infected three times via the conjunctiva at six- and twelve-week intervals by applying either 1 × 10(4) or 1 × 10(6) inclusion-forming units (IFUs) of C. caviae. Ocular pathology, infection course, C. caviae-specific serum IgG levels and their capacity to bind and neutralize infection ex vivo were assessed. Animals infected with 1 × 10(4) IFUs had completely diminished ocular infection and pathology after the 2nd infection with increased levels of C. caviae-specific serum IgG and their effective capacity to bind and neutralize C. caviae. Only partial protection was observed in animals infected with 1 × 10(6) IFUs after the 2nd and 3rd infections. Our findings show that full protection was observed in animals repeatedly infected with the lower dose. The lower dose appeared not to compromise the host immune system, thereby enabling fast clearance of the pathogen and the establishment of competent neutralizing antibodies.