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Infectious Ocular Disorders and Molecular Analysis
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Infectious Ocular Disorders and Molecular Analysis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 22389

Special Issue Editors

Dr. Sunao Sugita

E-Mail Website
Guest Editor
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan
Interests: ocular immunology; ocular infection; herpesvirus, uveitis, T cells; retinal degeneration; iPS cells; transplantation; immune rejection
Dr. Yoko Futatsugi

E-Mail Website
Guest Editor
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan
Interests: ocular immunology; uveitis; ES/iPS cells; transplantation; immune rejection; T cells; human leukocyte antigen; autoimmune disease

Special Issue Information

Dear Colleagues,

Pathogen detection is important in the diagnosis and diagnosis-based treatment of infectious ocular disorders. However, it is difficult to detect pathogens because of the small amounts of samples obtained from the ocular region. Therefore, a method to detect such pathogens with high sensitivity/specifity and rapidity from a small amount of specimen is required for the diagnosis of ocular infections. In addition, the pathogens include bacteria, fungi, viruses, and parasites. Recently, polymerase chain reaction (PCR) diagnosis using local ocular specimens has become indispensable in the treatment of infectious uveitis, kerititis, and retinitis. Other molecular analyses such as genome sequence analysis, metagenome analysis, and so on have also been performed on those specimens in basic reseach.

Our reserch group developed the first PCR examination system in the ophthalmology field. We showed clinical applications of multiplex PCR (for the detection of, e.g., herpesvirus DNA) and broad-range PCR (for the detection of, e.g., bacteria 16S rDNA) to the specimens from eye infection. These advancements in PCR-based examination are still making a great contribution to our field. Our fellows also established a novel multiplex PCR, termed strip PCR prototype, for detecting 24 pathogens responsible for ocular infections. We further enhanced the technique by developing direct strip PCR that skips DNA extraction in the procedure. This PCR is anticipated to provide easier etiological evaluation even for general ophthalmologists, through the detection of more pathogens from ocular samples of infectious uveitis patients.

Therefore, this Special Issue of IJMS will focus on advances in the field of infectious ocular disorders by molecular analyses, including general PCR, real-time PCR, multiplex PCR, genome analysis, and so on. The target disorders are broad ocular infections such as keratitis, ocular surface infectious diseases (e.g., conjunctivitis), corneal endothelitis, uveitis, retinitis, and endophthalmitis. We are seeking novel research in the field of such molecular analyses on infectious ocular disorders. Our aim is for this Special Issue to shed light on multidisciplinary researchs that examine infection in the eye using new molecular analyses.

Dr. Sunao Sugita
Dr. Yoko Futatsugi
Guest Editors

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Keywords

  • ocular infections
  • keratitis
  • ocular surface infectious diseases
  • corneal endotheliitis
  • uveitis
  • retinitis
  • endophthalmitis
  • herpesvirus
  • Polymerase chain reaction (PCR)
  • genome analysis

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Published Papers (7 papers)

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Research

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11 pages, 551 KiB  
Communication
Cytomegalovirus Glycoprotein B Genotype in Patients with Anterior Segment Infection
by Chu-Yen Huang, Yu-Chun Cheng, Yih-Shiou Hwang, Eugene Yu-Chuan Kang and Ching-Hsi Hsiao
Int. J. Mol. Sci. 2023, 24(7), 6304; https://doi.org/10.3390/ijms24076304 - 27 Mar 2023
Viewed by 1468
Abstract
(1) The glycoprotein B (gB) on the viral envelope, encoded by the most widely characterised polymorphic gene, gpUL55, is responsible for cytomegalovirus (CMV) entry into the host and could serve as a potential marker of pathogenicity. The aim of the present study [...] Read more.
(1) The glycoprotein B (gB) on the viral envelope, encoded by the most widely characterised polymorphic gene, gpUL55, is responsible for cytomegalovirus (CMV) entry into the host and could serve as a potential marker of pathogenicity. The aim of the present study is to investigate the distribution of the CMV gB genotype in anterior segment infection in Taiwan and its correlation with clinical manifestations and outcomes. (2) Fifty-seven patients with CMV anterior segment infection were identified according to clinical features and positivity for CMV DNA in aqueous humour samples. CMV gB genotyping was performed through polymerase chain reaction assays. Patients’ medical records were retrospectively reviewed. (3) Among the 57 aqueous humour samples tested for gB, 40 (70.28%) had multiple gB genotypes, and only 17 (29.82%) had a single gB genotype. Compared with single-genotype infection, multiple-genotype infection was correlated with higher CMV loads (p < 0.001) but not correlated with outcome. A higher proportion of patients with the gB3 genotype had received filtering surgery before antiviral treatment than those without the gB3 genotype (p = 0.046). (4) Multiple-genotype infection was highly prevalent in CMV anterior segment infection in Taiwan, and gB1 and gB3 were predominant. Multiple-genotype infection was correlated with higher CMV loads but not with specific clinical manifestations or prognostic outcomes. The gB3 genotype may be correlated with poor intraocular pressure control. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
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13 pages, 1486 KiB  
Article
Detection of Mycoplasma Contamination in Transplanted Retinal Cells by Rapid and Sensitive Polymerase Chain Reaction Test
by Sunao Sugita, Ayumi Hono, Shoko Fujino, Yoko Futatsugi, Yuta Yunomae, Norio Shimizu and Masayo Takahashi
Int. J. Mol. Sci. 2021, 22(22), 12555; https://doi.org/10.3390/ijms222212555 - 21 Nov 2021
Cited by 7 | Viewed by 4269
Abstract
Contamination of cells/tissues by infectious pathogens (e.g., fungi, viruses, or bacteria, including mycoplasma) is a major problem in cell-based transplantation. In this study, we tested a polymerase chain reaction (PCR) method to provide rapid, simple, and sensitive detection of mycoplasma contamination in laboratory [...] Read more.
Contamination of cells/tissues by infectious pathogens (e.g., fungi, viruses, or bacteria, including mycoplasma) is a major problem in cell-based transplantation. In this study, we tested a polymerase chain reaction (PCR) method to provide rapid, simple, and sensitive detection of mycoplasma contamination in laboratory cultures for clinical use. This mycoplasma PCR system covers the Mycoplasma species (spp.) listed for testing in the 17th revision of the Japanese Pharmacopoeia, and we designed it for use in transplantable retinal cells. Here, we analyzed mycoplasma contamination in induced pluripotent stem cell (iPS cell)-derived transplantable retinal pigment epithelium (RPE) cells. In the spike tests to RPE cells with nine species of class Mollicutes bacteria, including seven Mycoplasma spp. and one of each Acholeplasma spp. and Ureaplasma spp., contamination at the concentration of 100 and 10 CFU/mL were detected with 100% probability in all cases, while 1 CFU/mL had a detection rate of 0–75%. DNA prepared from bacteria species other than class Mollicutes species was not detectable, indicating the specificity of this PCR. While iPS cells and iPS-RPE cells established in our laboratory were all negative by this PCR, some of the commercially available cell lines were positive. Cells for transplantation should never have infection, as once pathogens are implanted into the eyes, they can cause severe intraocular inflammation. Thus, it is imperative to monitor for infections in the transplants, although generally, mycoplasma infection is difficult to detect. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
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Graphical abstract

15 pages, 2759 KiB  
Article
Role Played by Receptors for Advanced Glycosylation End Products in Corneal Endothelial Cells after HSV-1 Infection
by Dai Miyazaki, Michiko Kandori-Inoue, Yumiko Shimizu, Fumie Ohtani, Ikuyo Chono, Yoshitsugu Inoue and Satoru Yamagami
Int. J. Mol. Sci. 2021, 22(11), 5833; https://doi.org/10.3390/ijms22115833 - 29 May 2021
Cited by 2 | Viewed by 2849
Abstract
Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by [...] Read more.
Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by the receptors for the AGEs (RAGE) and are manifested as a type I interferon response. Interestingly, in our study, human corneal endothelial cells (HCEn) cells did not respond to the typical RAGE ligands, including the AGEs, high mobility group box 1 (HMGB1), and serum amyloid-A (SAA). Instead, HCEn cells responded exclusively to the CpG DNA, which is possessed by typical corneal pathogen, herpes simplex virus-1 (HSV-1). Upon HSV-1 infection, the surface expression of RAGE was increased, and endocytosed HSV-1 was associated with RAGE and CpG DNA receptor, TLR9. RAGE DNA transfection markedly increased interferon-β secretion by CpG DNA or HSV-1 infection. HSV-1 infection-induced interferon-β secretion was abolished by TLR9 inhibition and partially by RAGE inhibition. Global transcriptional response analysis confirmed that RAGE and TLR9 were both significantly involved in type I interferon responses. We conclude that RAGE is a sensor of HSV-1 infection and provokes a type I interferon response. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
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16 pages, 1751 KiB  
Article
Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals
by Nobuyo Yawata, Mariko Shirane, Kaing Woon, Xinru Lim, Hidenori Tanaka, Yoh-Ichi Kawano, Makoto Yawata, Soon-Phaik Chee, Jay Siak and Koh-Hei Sonoda
Int. J. Mol. Sci. 2021, 22(7), 3623; https://doi.org/10.3390/ijms22073623 - 31 Mar 2021
Cited by 6 | Viewed by 2522
Abstract
Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed [...] Read more.
Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor–ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor–ligand interactions. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
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Review

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11 pages, 897 KiB  
Review
Role of Recent PCR Tests for Infectious Ocular Diseases: From Laboratory-Based Studies to the Clinic
by Sunao Sugita, Hiroshi Takase and Satoko Nakano
Int. J. Mol. Sci. 2023, 24(9), 8146; https://doi.org/10.3390/ijms24098146 - 2 May 2023
Cited by 4 | Viewed by 2562
Abstract
Infectious uveitis is a vision-threatening condition that requires prompt clinical diagnosis and proper treatment. However, rapid and proper diagnosis in infectious uveitis remains challenging. Several examination tests, including polymerase chain reaction (PCR) tests, are transitioning from laboratory-based basic research-level tests to bedside clinical [...] Read more.
Infectious uveitis is a vision-threatening condition that requires prompt clinical diagnosis and proper treatment. However, rapid and proper diagnosis in infectious uveitis remains challenging. Several examination tests, including polymerase chain reaction (PCR) tests, are transitioning from laboratory-based basic research-level tests to bedside clinical tests, and recently tests have changed to where they can be performed right next to clinicians. In this review, we introduce an updated overview of recent studies that are representative of the current trends in clinical microbiological techniques including PCR tests for infectious uveitis. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
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13 pages, 286 KiB  
Review
Update on Current Microbiological Techniques for Pathogen Identification in Infectious Endophthalmitis
by Lindsay Y. Chun, Donavon J. Dahmer, Shivam V. Amin, Seenu M. Hariprasad and Dimitra Skondra
Int. J. Mol. Sci. 2022, 23(19), 11883; https://doi.org/10.3390/ijms231911883 - 6 Oct 2022
Cited by 4 | Viewed by 2107
Abstract
Infectious endophthalmitis is a vision-threatening medical emergency that requires prompt clinical diagnosis and the initiation of treatment. However, achieving precision in endophthalmitis management remains challenging. In this review, we provide an updated overview of recent studies that are representative of the current trends [...] Read more.
Infectious endophthalmitis is a vision-threatening medical emergency that requires prompt clinical diagnosis and the initiation of treatment. However, achieving precision in endophthalmitis management remains challenging. In this review, we provide an updated overview of recent studies that are representative of the current trends in clinical microbiological techniques for infectious endophthalmitis. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
24 pages, 1358 KiB  
Review
Therapeutic Approaches for Age-Related Macular Degeneration
by Ruth M. Galindo-Camacho, Cristina Blanco-Llamero, Raquel da Ana, Mayra A. Fuertes, Francisco J. Señoráns, Amélia M. Silva, María L. García and Eliana B. Souto
Int. J. Mol. Sci. 2022, 23(19), 11769; https://doi.org/10.3390/ijms231911769 - 4 Oct 2022
Cited by 17 | Viewed by 5119
Abstract
Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there [...] Read more.
Damage to the retinal pigment epithelium, Bruch’s membrane and/or tissues underlying macula is known to increase the risk of age-related macular degeneration (AMD). AMD is commonly categorized in two distinct types, namely, the nonexudative (dry form) and the exudative (wet form). Currently, there is no ideal treatment available for AMD. Recommended standard treatments are based on the use of vascular endothelial growth factor (VEGF), with the disadvantage of requiring repeated intravitreal injections which hinder patient’s compliance to the therapy. In recent years, several synthetic and natural active compounds have been proposed as innovative therapeutic strategies against this disease. There is a growing interest in the development of formulations based on nanotechnology because of its important role in the management of posterior eye segment disorders, without the use of intravitreal injections, and furthermore, with the potential to prolong drug release and thus reduce adverse effects. In the same way, 3D bioprinting constitutes an alternative to regeneration therapies for the human retina to restore its functions. The application of 3D bioprinting may change the current and future perspectives of the treatment of patients with AMD, especially those who do not respond to conventional treatment. To monitor the progress of AMD treatment and disease, retinal images are used. In this work, we revised the recent challenges encountered in the treatment of different forms of AMD, innovative nanoformulations, 3D bioprinting, and techniques to monitor the progress. Full article
(This article belongs to the Special Issue Infectious Ocular Disorders and Molecular Analysis)
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