Ab Interno Ahmed Glaucoma Valve Plugs In An Eye With Persistent Hypotony.

PURPOSE: This case report aims to describe a new method for increasing intraocular pressure (IOP) in patients with acute hypotony resulting from uveitis flare-ups and preexisting glaucoma drainage devices. The temporary glaucoma tube plug method described is effective and safe. METHODS: This case report presents a 47-year-old female patient with a history of chronic panuveitis and secondary glaucoma, who had 2 previously implanted Ahmed glaucoma valves. The patient developed panuveitis flare-up and persistent hypotony. A novel method of ab interno plugging of the glaucoma tubes using 2-0 prolene suture plugs was performed. Following treatment, the IOP increased successfully and remained within the normal range. CONCLUSION: The temporary ab interno glaucoma tube plug method effectively increased IOP in a patient with 2 preimplanted Ahmed glaucoma valves with persistent low IOP due to uveitis.

Acute macular infarctions in pediatric patients with hemoglobin SS disease.

Purpose: To report two cases of symptomatic posterior pole arterial occlusions in patients with hemoglobin SS disease. Observations: Two teenage patients with hemoglobin SS disease presented with visual distortions, and on dilated fundus examination and testing, they were found to have arterial occlusions involving the posterior pole. The patients were evaluated for stroke with head imaging and received exchange transfusion by hematology. Conclusions and Importance: This case series reports the unusual findings of arterial occlusions in the posterior pole resulting in areas of retinal whitening and ischemia in patients with HbSS. While sickle cell retinopathy is typically considered a peripheral retinal disease, these findings underscore the importance of vigilance when examining patients with sickle cell disease.

Diabetes Exacerbates Pseudomonas aeruginosa Keratitis in Streptozotocin-Induced and db/db Mice via Altering Programmed Cell Death Pathways.

Purpose: Patients with diabetes have a higher incidence of infections, which are often more severe. This study aimed to investigate the impact of hyperglycemia on bacterial keratitis caused by Pseudomonas aeruginosa (Pa) in two mouse models of diabetes, streptozotocin-induced type 1 diabetes mellitus (T1DM) and db/db type 2 diabetes mellitus. Methods: The susceptibility of corneas to Pa was assessed by determining the inocula required to cause infectious keratitis. Dead or dying cells were identified using TUNEL staining or immunohistochemistry. Specific inhibitors were used to evaluate the role of cell death modulators in Pa keratitis. Cytokines and Treml4 expressions were analyzed using quantitative PCR, and the role of Treml4 in keratitis was determined using small interfering RNA technology. Results: DM corneas required significantly fewer inocula to develop Pa keratitis, with T1DM corneas requiring 750 inocula and type 2 diabetes mellitus corneas requiring 2000 inocula, compared with 10,000 inocula required for normal (NL) mice. T1DM corneas had more TUNEL-positive and fewer F4/80-positive cells than NL corneas. Phospho-caspase 8 (apoptosis) and -RIPK3 (necroptosis) staining was more intense in the epithelial and stromal layers of NL and T1DM corneas, respectively. Pa keratitis was augmented by targeting caspase-8 and prevented by RIPK3 inhibition in both NL and T1DM mice. Hyperglycemia suppressed IL-17A/F and augmented IL-17C, IL-1ß, IL-1Ra, and TREML4, the downregulation of which protected T1DM corneas from Pa infection by suppressing necroptosis. RIPK3 inhibition blocked Pa infection in db/+ mice and significantly decreased the severity of keratitis in db/db mice. Conclusions: Hyperglycemia exacerbates bacterial keratitis in B6 mice by skewing apoptosis toward necroptosis. Preventing or reversing this transition may serve as an adjunct therapy for treating microbial keratitis in patients with diabetes.

IL-36α Enhances Host Defense against Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas.

The IL-36 cytokines are known to play various roles in mediating the immune response to infection in a tissue- and pathogen-dependent manner. The present study seeks to investigate the role of IL-36R signaling in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. IL-36α-/-, IL-36γ-/-, and IL-36R-/- mice had significantly more severe keratitis than wild-type mice. At six hours postinfection, IL-36α pretreatment augmented P. aeruginosa-induced expression of IL-1Ra, IL-36γ, LCN2, and S100A8/A9. At one day postinfection, exogenous IL-36α suppressed, whereas IL-36α deficiency promoted, the expression of IL-1ß. At three days postinfection, exogenous IL-36α suppressed Th1 but promoted Th2 immune response. IL-36α stimulated the infiltration of IL-22-expressing immune cells, and IL-22 neutralization resulted in more severe keratitis. IL-36α alone stimulated dendritic cell infiltration in B6 mouse corneas. Taken together, our study suggests that IL-36R signaling plays a protective role in the pathogenesis of P. aeruginosa keratitis by promoting the innate immune defense, Th2, and/or Th22/IL-22 immune responses. Exogenous IL-36α might be a potential therapy for improving the outcome of P. aeruginosa keratitis.

Role of IL-36γ/IL-36R Signaling in Corneal Innate Defense Against Candida albicans Keratitis.

Purpose: Interleukin (IL)-36 cytokines have been shown to play either beneficial or detrimental roles in the infection of mucosal tissues in a pathogen-dependent manner, but their involvement in fungal keratitis remains elusive. We herein investigated their expression and function in mediating corneal innate immunity against Candida albicans infection. Methods: Gene expression in mouse corneas with or without C. albicans infection was determined by regular RT- and real-time (q)-PCR, Western blot analysis, ELISA or proteome profile assay. The severity of C. albicans keratitis was assessed using clinical scoring, bacterial counting, and myeloperoxidase (MPO) activity as an indicator of neutrophil infiltration. IL36R knockout mice and IL-33-specific siRNA were used to assess the involvement IL-33 signaling in C. albicans-infected corneas. B6 CD11c-DTR mice and clodronate liposomes were used to define the involvement of dendritic cells (DCs) and macrophages in IL-36R signaling and C. albicans keratitis, respectively. Results: IL-36γ were up-regulated in C57BL6 mouse corneas in response to C. albicans infection. IL-36 receptor-deficient mice display increased severity of keratitis, with a higher fungal load, MPO, and IL-1ß levels, and lower soluble sIL-1Ra and calprotectin levels. Exogenous IL-36γ prevented fungal keratitis pathogenesis with lower fungal load and MPO activity, higher expression of sIL-1Ra and calprotectin, and lower expression of IL-1ß, at mRNA or protein levels. Protein array analysis revealed that the expression of IL-33 and REG3G were related to IL-36/IL36R signaling, and siRNA downregulation of IL-33 increased the severity of C. albicans keratitis. Depletion of dendritic cells or macrophages resulted in severe C. albicans keratitis and yet exhibited minimal effects on exogenous IL-36γ-induced protection against C. albicans infection in B6 mouse corneas. Conclusions: IL-36/IL36R signaling plays a protective role in fungal keratitis by promoting AMP expression and by suppressing fungal infection-induced expression of proinflammatory cytokines in a dendritic cell- and macrophage-independent manner.

ISG15 Acts as a Mediator of Innate Immune Response to Pseudomonas aeruginosa Infection in C57BL/6J Mouse Corneas.

Purpose: IFN-stimulated gene (ISG) 15 is a type 1 IFN-induced protein and known to modify target proteins in a manner similar to ubiquitylation (protein conjugation by ISG15 is termed ISGylation). We sought to determine the role of ISG15 and its underlying mechanisms in corneal innate immune defense against Pseudomonas aeruginosa keratitis. Methods: ISG15 expression in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR and Western blot analysis. Gene knockout mice were used to define the role of ISG15 signaling in controlling the severity of P. aeruginosa keratitis, which was assessed with photographing, clinical scoring, bacterial counting, myeloperoxidase assay, and quantitative PCR determination of cytokine expression. Integrin LFA-1 inhibitor was used to assess its involvement of ISG15 signaling in P. aeruginosa-infected corneas. Results: Heat-killed P. aeruginosa induced ISG15 expression in cultured HCECs and accumulation in the conditioned media. Isg15 deficiency accelerated keratitis progress, suppressed IFNγ and CXCL10, and promoted IL-1ß while exhibiting no effects on IFNα expression. Moreover, exogenous ISG15 protected the corneas of wild-type mice from P. aeruginosa infection while markedly reducing the severity of P. aeruginosa keratitis in type 1 IFN-receptor knockout mice. Exogenous ISG15 increased bacteriostatic activity of B6 mouse corneal homogenates, and inhibition of LFA-1 exacerbated the severity of and abolished protective effects of ISG15 on P. aeruginosa keratitis. Conclusions: Type 1 INF-induced ISG15 regulates the innate immune response and greatly reduces the susceptibility of B6 mouse corneas to P. aeruginosa infection in an LFA-1-dependent manner.

Role of VIP and Sonic Hedgehog Signaling Pathways in Mediating Epithelial Wound Healing, Sensory Nerve Regeneration, and Their Defects in Diabetic Corneas.

Diabetic keratopathy, a sight-threatening corneal disease, comprises several symptomatic conditions including delayed epithelial wound healing, recurrent erosions, and sensory nerve (SN) neuropathy. We investigated the role of neuropeptides in mediating corneal wound healing, including epithelial wound closure and SN regeneration. Denervation by resiniferatoxin severely impaired corneal wound healing and markedly upregulated proinflammatory gene expression. Exogenous neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) partially reversed resiniferatoxin's effects, with VIP specifically inducing interleukin-10 expression. Hence, we focused on VIP and observed that wounding induced VIP and VIP type 1 receptor (VIPR1) expression in normal (NL) corneas, but not corneas from mice with diabetes mellitus (DM). Targeting VIPR1 in NL corneas attenuated corneal wound healing, dampened wound-induced expression of neurotrophic factors, and exacerbated inflammatory responses, while exogenous VIP had the opposite effects in DM corneas. Remarkably, wounding and diabetes also affected the expression of Sonic Hedgehog (Shh) in a VIP-dependent manner. Downregulating Shh expression in NL corneas decreased while exogenous Shh in DM corneas increased the rates of corneal wound healing. Furthermore, inhibition of Shh signaling dampened VIP-promoted corneal wound healing. We conclude that VIP regulates epithelial wound healing, inflammatory response, and nerve regeneration in the corneas in an Shh-dependent manner, suggesting a therapeutic potential for these molecules in treating diabetic keratopathy.

IL-17 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas.

The aim of this study was to elucidate the expression and functions of IL-17 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. We found that P. aeruginosa infection induced and increased signaling of IL-23/23R/17/17R in mouse corneas. Targeting IL-17A or the IL-17A-specific receptor IL-17RA/IL-17RC with neutralizing Abs resulted in a significant decrease in the severity of P. aeruginosa keratitis, including a decrease in bacterial burden and polymorphonuclear leukocyte infiltration. IL-17A-signaling blockade also significantly reduced the expression of the proinflammatory cytokines L-1ß, IL-24, and MMP-13 and increased the expression of the anti-inflammatory cytokine IL-1RA in mouse corneal epithelium. The presence of mouse IL-17A exacerbated P. aeruginosa-mediated tissue destruction. A cytokine protein array revealed that the expression of osteoprotegerin (OPG) was regulated by IL-17A, and OPG neutralization also resulted in a decrease in the severity of P. aeruginosa keratitis. Although both IL-17 and OPG affected the balanced expression of IL-1ß and IL-1RA, only IL-17 inhibited the expression of TH2 cytokines. Taken together, our results revealed that IL-17A, along with its downstream factor OPG, plays a detrimental role in the pathogenesis of P. aeruginosa keratitis. Targeting IL-17A and/or the OPG/RANKL/RANK/TRAIL system is a potential therapeutic strategy in controlling the outcome of P. aeruginosa keratitis, which was demonstrated by concurrent topical application of IL-17A-neutralizing Ab and ciprofloxacin in B6 mice.

Substance P inhibits high urea-induced apoptosis through the AKT/GSK-3ß pathway in human corneal epithelial cells.

To investigate the effect of substance P (SP) on human corneal epithelial cells (HCECs) that have been stressed by a high urea environment and to determine the relationship between SP and the protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway. An in vitro model of chronic renal failure (CRF)-related dry eye was used to study HCECs that were treated with high urea concentrations. Cell proliferation was assayed using a cell counting kit-8 test. Besides, cell apoptosis was evaluated by flow cytometry. Furthermore, the effects of SP and the AKT inhibitor perifosine on the urea-treated HCECs were examined using immunofluorescence, quantitative real time polymerase chain reaction (qRT-PCR), and Western blot analysis. SP markedly reduced the number of apoptotic HCECs and decreased the cleaved caspase-3 expression levels while contributing to increased cellular proliferation (P < 0.05). The Western blot analysis and qRT-PCR experiments revealed that SP significantly increased the expression of p-AKT and p-GSK-3ß (P < 0.05); additionally, these increases were attenuated after the perifosine inhibition of the AKT signaling pathway (P < 0.05). These in vitro experiments demonstrated that SP may protect against the apoptotic damage of HCECs caused by the high urea condition. The underlying mechanism may be related to the activation of the AKT/GSK-3ß signaling pathway.

Opposing Effects of Neuropilin-1 and -2 on Sensory Nerve Regeneration in Wounded Corneas: Role of Sema3C in Ameliorating Diabetic Neurotrophic Keratopathy.

The diabetic cornea exhibits pathological alterations, such as delayed epithelial wound healing and nerve regeneration. We investigated the role of semaphorin (SEMA) 3C in corneal wound healing and reinnervation in normal and diabetic B6 mice. Wounding induced the expression of SEMA3A, SEMA3C, and their receptor neuropilin-2 (NRP2), but not NRP1, in normal corneal epithelial cells; this upregulation was suppressed for SEMA3C and NRP2 in diabetic corneas. Injections of Sema3C-specific small interfering RNA and NRP2-neutralizing antibodies in wounded mice resulted in a decrease in the rate of wound healing and regenerating nerve fibers, whereas exogenous SEMA3C had opposing effects in diabetic corneas. NRP1 neutralization, on the other hand, decreased epithelial wound closure but increased sensory nerve regeneration in diabetic corneas, suggesting a detrimental role in nerve regeneration. Taken together, epithelium-expressed SEMA3C plays a role in corneal epithelial wound closure and sensory nerve regeneration. The hyperglycemia-suppressed SEMA3C/NRP2 signaling may contribute to the pathogenesis of diabetic neurotrophic keratopathy, and SEMA3C might be used as an adjunctive therapeutic for treating the disease.

TSLP Protects Corneas From Pseudomonas aeruginosa Infection by Regulating Dendritic Cells and IL-23-IL-17 Pathway.

Purpose: We sought to determine the role of epithelium-produced thymic stromal lymphopoietin (TSLP) and its underlying mechanisms in corneal innate immune defense against Pseudomonas (P.) aeruginosa keratitis. Methods: The expression of TSLP and TSLPR in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR, Western, and/or ELISA. Cellular localization of TSLP receptor (TSLPR) was determined by whole mount confocal microscopy. TSLP-TSLPR signaling was downregulated by neutralizing antibodies and/or small interfering (si)RNA; their effects on the severity of P. aeruginosa-keratitis and cytokine expression were assessed using clinical scoring, bacterial counting, PMN infiltration, and real-time PCR. The role of dendritic cells (DCs) in corneal innate immunity was determined by local DC depletion using CD11c-DTR mice. Results: P. aeruginosa-infection induced the expression of TSLP and TSLPR in both cultured primary HCECs and in C57BL/6 mouse corneas. While TSLP was mostly expressed by epithelial cells, CD11c-positive cells were positive for TSLPR. Targeting TSLP or TSLPR with neutralizing antibodies or TSLPR with siRNA resulted in more severe keratitis, attributable to an increase in bacterial burden and PMN infiltration. TSLPR neutralization significantly suppressed infection-induced TSLP and interleukin (IL)-17C expression and augmented the expression of IL-23 and IL-17A. Local depletion of DCs markedly increased the severity of keratitis and exhibited no effects on TSLP and IL-23 expression while suppressing IL-17A and C expression in P. aeruginosa-infected corneas. Conclusions: The epithelium-expressed TSLP plays a protective role in P. aeruginosa keratitis through targeting of DCs and in an IL-23/IL-17 signaling pathway-related manner.

Opposing Effects of IL-1Ra and IL-36Ra on Innate Immune Response to Pseudomonas aeruginosa Infection in C57BL/6 Mouse Corneas.

Pseudomonas aeruginosa keratitis is characterized by severe corneal ulceration and may lead to blindness if not treated properly in a timely manner. Although the roles of the IL-1 subfamily of cytokines are well established, as a newly discovered subfamily, IL-36 cytokine regulation, immunological relevance, and relation with IL-1 cytokines in host defense remain largely unknown. In this study, we showed that P. aeruginosa infection induces the expression of IL-36α and IL-36γ, as well as IL-1ß and secreted IL-1Ra (sIL-1Ra), but not IL-36Ra. Downregulation of IL-1Ra increases, whereas downregulation of IL-36Ra decreases the severity of P. aeruginosa keratitis. IL-1R and IL-36Ra downregulation have opposing effects on the expression of IL-1ß, sIL-1Ra, IL-36γ, S100A8, and CXCL10 and on the infiltration of innate immune cells. Administration of recombinant IL-1Ra improved, whereas IL-36Ra worsened the outcome of P. aeruginosa keratitis. Local application of IL-36γ stimulated the expression of innate defense molecules S100A9, mouse ß-defensin 3, but suppressed IL-1ß expression in B6 mouse corneas. IL-36γ diminished the severity of P. aeruginosa keratitis, and its protective effects were abolished in the presence of S100A9 neutralizing Ab and partially affected by CXCL10 and CXCR3 neutralizations. Thus, our data reveal that IL-1Ra and IL-36Ra have opposing effects on the outcome of P. aeruginosa keratitis and suggest that IL-36 agonists may be used as an alternative therapeutic to IL-1ß-neutralizing reagents in controlling microbial keratitis and other mucosal infections.

Crosslinking Enzyme Lysyl Oxidase Modulates Scleral Remodeling in Form-Deprivation Myopia.

PURPOSE: Scleral remodeling causes the excessive ocular elongation that underlies myopia. Lysyl oxidase (LOX), a copper-containing amine oxidase, can catalyze collagen and elastin crosslinking. The purpose of this study was to investigate the role of LOX in scleral remodeling in form-deprivation myopia (FDM). METHODS: Seventy-five guinea pigs were randomly divided into five groups as follows: a normal control group, an FDM group, an FDM plus ß-aminopropionitrile (BAPN) group, an FDM plus TGF-ß1 (TGF-ß1) group, and an FDM plus vehicle group. A translucent diffuser was used to induce FDM, and intravitreal injection was used to administer BAPN, TGF-ß1 or vehicle. The scleral LOX and collagen gene and protein levels and the posterior scleral ultrastructure and biomechanics were measured. RESULTS: In the FDM group, both the scleral LOX and collagen gene and protein levels were significantly lower than those in the control eyes. The collagen fibril diameters were significantly decreased in the FDM group compared with the diameters in the control group. A significant decrease in LOX gene and protein expression was observed after BAPN injection, and an increase was observed after TGF-ß1 treatment compared with the levels in the FDM group. Additionally, the scleral collagen fibrils were significantly decreased in the BAPN-treated eyes but increased in the TGF-ß1-treated eyes compared with the FDM eyes. The ultimate stress and Young's modulus of the sclera were lowest in the BAPN group, followed by the FDM group and the TGF-ß1 group. The ultimate strain (%) of the sclera was lowest in the TGF-ß1 group, followed by the FDM group and the BAPN group. CONCLUSION: LOX expression was significantly lowered in myopic sclera. Modulating LOX expression induced a change in both the scleral collagen fibril diameter and the scleral biomechanics. Therefore, LOX may play a key role in the myopia scleral remodeling procedure.

Interaction between Corneal and Internal Ocular Aberrations Induced by Orthokeratology and Its Influential Factors.

PURPOSE: To investigate the interaction between corneal, internal, and total wavefront aberrations (WAs) and their influential factors during orthokeratology (OK) treatment in Chinese adolescents. METHODS: Thirty teenagers (n = 30 eyes) were enrolled in the study; spherical equivalent refraction (SE), corneal curvature radius (CCR), central corneal thickness (CCT), WAs, and the difference in limbal transverse diameter and OK lens diameter (ΔLLD) were detected before and after one-month OK treatment. Every component of WAs was measured simultaneously by iTrace aberrometer. The influential factors of OK-induced WAs were analyzed. RESULTS: SE and CCT decreased while CCR increased significantly (P < 0.01). Higher-order aberrations (HOAs), Spherical aberrations (SAs), and coma increased significantly (P < 0.01). Corneal horizontal coma (Z31-C) and corneal spherical aberrations (Z40-C) increased (P < 0.01). The HOAs, coma, SAs, Z31-C, Z31-T, Z40-C, and Z40-T were positively correlated with SE and CCR (P < 0.01). Z3-1-C showed negative correlations with (ΔLLD) and positive correlations with SE (P < 0.05). CONCLUSIONS: The increase in OK-induced HOAs is mainly attributed to Z31 and Z40 of cornea. Z3-1 in the internal component showed a compensative effect on the corneal vertical coma. The degree of myopic correction and increase in CCR may be the essential influential factors of the increase in Z31 and Z40. The appropriate size of the OK lens may be helpful to decrease OK-induced vertical coma.

Effects of Tear Film Lipid Layer Thickness and Blinking Pattern on Tear Film Instability After Corneal Refractive Surgery.

PURPOSE: To investigate associations between changes in tear film instability and the lipid layer thickness (LLT) and blink pattern after corneal refractive surgery (CRS). METHODS: Forty patients were enrolled in this study. The LLT and blink pattern were evaluated 1 week before and 30 days after CRS using a novel interferometer and an ocular surface disease index (OSDI) questionnaire, and other tear film stability markers were also evaluated. RESULTS: Mean OSDI scores increased from 5.52 to 8.54 (P = 0.016), corneal fluorescence staining scores increased from 0.05 to 0.25 (P = 0.034), first noninvasive tear breakup time (NIBUT-F) decreased from 9.66 to 7.33 seconds (P = 0.014), and average noninvasive tear breakup time (NIBUT-Ave) decreased from 12.32 to 10.26 seconds (P = 0.047) 1 month after CRS. Meanwhile, mean total blink frequency in 20 seconds decreased significantly from 12.62 to 6.31 (P < 0.001); LLT did not change significantly (P = 0.447). The change in NIBUT-Ave was positively correlated with that in LLT (P = 0.003) and negatively correlated with that in the partial blink rate (P = 0.013). The changes in the OSDI questionnaire, NIBUT, LLT, and blink pattern were not different between the laser-assisted in situ keratomileusis and laser-assisted subepithelial keratomileusis groups. CONCLUSIONS: A decrease in tear film stability occurs 1 month after CRS, the change in the blink pattern and unchanged LLT preoperatively and postoperatively suggesting that these parameters play a role in maintaining tear film stability after CRS.

Expression of Wnt/ß-Catenin Signaling Pathway and Its Regulatory Role in Type I Collagen with TGF-ß1 in Scleral Fibroblasts from an Experimentally Induced Myopia Guinea Pig Model.

Background. To investigate Wnt/ß-catenin signaling pathway expression and its regulation of type I collagen by TGF-ß1 in scleral fibroblasts from form-deprivation myopia (FDM) guinea pig model. Methods. Wnt isoforms were examined using genome microarrays. Scleral fibroblasts from FDM group and self-control (SC) group were cultured. Wnt isoforms, ß-catenin, TGF-ß1, and type I collagen expression levels were examined in the two groups with or without DKK-1 or TGF-ß1 neutralizing antibody. Results. For genome microarrays, the expression of Wnt3 in FDM group was significantly greater as confirmed in retinal and scleral tissue. The expression of Wnt3 and ß-catenin significantly increased in FDM group and decreased significantly with DKK-1. TGF-ß1 expression level decreased significantly in FDM group and increased significantly with DKK-1. Along with morphological misalignment inside and outside cells, the amount of type I collagen decreased in FDM group. Furthermore, type I collagen increased and became regular in DKK-1 intervention group, whereas it decreased and rearranged more disorder in TGF-ß1 neutralizing antibody intervention group. Conclusions. The activation of Wnt3/ß-catenin signaling pathway was demonstrated in primary scleral fibroblasts in FDM. This pathway further reduced the expression of type I collagen by TGF-ß1, which ultimately played a role in scleral remodeling during myopia development.

Complete genome sequence of Klebsiella pneumoniae phage JD001.

Klebsiella pneumoniae is a member of the family Enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. The emergence of multidrug-resistant strains of K. pneumoniae has became a public health problem globally. To develop an effective antimicrobial agent, we isolated a bacteriophage, named JD001, from seawater and sequenced its genome. Comparative genome analysis of phage JD001 with other K. pneumoniae bacteriophages revealed that phage JD001 has little similarity to previously published K. pneumoniae phages KP15, KP32, KP34, and phiKO2. Here we announce the complete genome sequence of JD001 and report major findings from the genomic analysis.