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Emerging OMICS Approaches to Studying the Eye in the Norm and Pathology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 53757

Special Issue Editor

1. Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA
2. The Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA
Interests: analytical (bio)chemistry; biochemistry, physiology, and pathophysiology of the ocular surface; chemistry, biochemistry, and biophysics of lipids; chemistry, biochemistry, and biophysics of the tear film and meibum; drug discovery; enzymology; meibomian gland studies
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Special Issue Information

Dear Colleagues,

This Special Issue of IJMS is seeking articles that would provide new insights into the molecular aspects of physiology and biochemistry of the eye and adnexa, from an OMICS point of view. Submissions with an emphasis on emerging approaches, such as genomics, metabolomics/metabonomis, proteomics, lipidomics, and glycomics are welcome. The Special Issue will aim to present a broad view of the ocular surface, conjunctiva, cornea, retina, eyelids, meibomian and lacrimal glands, and other ocular structures in the norm and pathology. The molecular bases of diseases are often poorly understood, and so are the effects of aging, gender, diet, pharmaceutical intervention, etc. Obtaining and discussing new information on the molecular mechanisms of these processes, and the molecular differences between metabolomes, proteomes, lipidomes, and glycomes of healthy tissues, organs, and secretions, and those of patients with ocular pathologies, would be an important step toward finding cures for those conditions.

Dr. Igor Butovich
Guest Editor

Manuscript Submission Information

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Keywords

  • Eye
  • Meibomian Gland
  • Lacrimal Gland
  • Conjunctiva
  • Cornea
  • Retina
  • Ocular Surface
  • Metabolomics
  • Lipidomics
  • Proteomics
  • Genomics
  • Glycobiology

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Published Papers (11 papers)

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Research

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17 pages, 1152 KiB  
Article
Clinical and Genetic Analysis of a European Cohort with Pericentral Retinitis Pigmentosa
by Marianthi Karali, Francesco Testa, Raffaella Brunetti-Pierri, Valentina Di Iorio, Mariateresa Pizzo, Paolo Melillo, Maria Rosaria Barillari, Annalaura Torella, Francesco Musacchia, Luigi D’Angelo, Sandro Banfi and Francesca Simonelli
Int. J. Mol. Sci. 2020, 21(1), 86; https://doi.org/10.3390/ijms21010086 - 20 Dec 2019
Cited by 22 | Viewed by 3139
Abstract
Retinitis pigmentosa (RP) is a clinically heterogenous disease that comprises a wide range of phenotypic and genetic subtypes. Pericentral RP is an atypical form of RP characterized by bone-spicule pigmentation and/or atrophy confined in the near mid-periphery of the retina. In contrast to [...] Read more.
Retinitis pigmentosa (RP) is a clinically heterogenous disease that comprises a wide range of phenotypic and genetic subtypes. Pericentral RP is an atypical form of RP characterized by bone-spicule pigmentation and/or atrophy confined in the near mid-periphery of the retina. In contrast to classic RP, the far periphery is better preserved in pericentral RP. The aim of this study was to perform the first detailed clinical and genetic analysis of a cohort of European subjects with pericentral RP to determine the phenotypic features and the genetic bases of the disease. A total of 54 subjects from 48 independent families with pericentral RP, non-syndromic and syndromic, were evaluated through a full ophthalmological examination and underwent clinical exome or retinopathy gene panel sequencing. Disease-causative variants were identified in 22 of the 35 families (63%) in 10 different genes, four of which are also responsible for syndromic RP. Thirteen of the 34 likely pathogenic variants were novel. Intra-familiar variability was also observed. The current study confirms the mild phenotype of pericentral RP and extends the spectrum of genes associated with this condition. Full article
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20 pages, 9666 KiB  
Article
Comparative Transcriptomic and Lipidomic Analyses of Human Male and Female Meibomian Glands Reveal Common Signature Genes of Meibogenesis
by Igor A. Butovich, Nita Bhat and Jadwiga C. Wojtowicz
Int. J. Mol. Sci. 2019, 20(18), 4539; https://doi.org/10.3390/ijms20184539 - 13 Sep 2019
Cited by 20 | Viewed by 3064
Abstract
Meibum is a lipid secretion that is produced by holocrine Meibomian glands (MGs). MGs are a specialized type of sebaceous glands that are embedded in the human eyelids. Chemically, meibum and sebum are different. A detailed characterization of lipidome and transcriptome of MG [...] Read more.
Meibum is a lipid secretion that is produced by holocrine Meibomian glands (MGs). MGs are a specialized type of sebaceous glands that are embedded in the human eyelids. Chemically, meibum and sebum are different. A detailed characterization of lipidome and transcriptome of MG is required to deconvolute a complex and poorly characterized array of biosynthetic reactions (termed meibogenesis) that lead to formation of meibum. Changes in the composition and quality of meibum have been linked to various ocular disorders, some of which are more prevalent in males, while others in females. To establish the role of gender in meibogenesis in humans, we characterized MG transcriptomes and lipidomes of females and males, and identified signature genes of meibogenesis in both genders. Specimens of MG tissues were subjected to mRNA microarray analyses. Chemical composition of meibum samples was assessed chromatographically and mass spectrometrically. Both targeted and untargeted approaches were used. About 290 signature genes of meibogenesis were identified. The analyses of their expression patterns demonstrated no major differences between the genders. Lipid profiling of major classes of meibomian lipids, such as wax esters, cholesteryl esters, free cholesterol, (O)-acylated omega-hydroxy fatty acids (OAHFA), cholesteryl esters of OAHFA, and triacylglycerols, also demonstrated only minor (and random) differences in these lipids. The results of transcriptomic analyses correlated well with lipidomic data. Taken together, our data imply that in males and females, meibogenesis proceeds in a similar fashion, yielding secretions with similar, highly conserved, compositions. This finding is important for designing novel, gender-independent diagnostic and therapeutic approaches to various MG-related diseases and pathological conditions. Full article
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14 pages, 1523 KiB  
Article
Multi-Omics Approach for Studying Tears in Treatment-Naïve Glaucoma Patients
by Claudia Rossi, Ilaria Cicalini, Maria Concetta Cufaro, Luca Agnifili, Leonardo Mastropasqua, Paola Lanuti, Marco Marchisio, Vincenzo De Laurenzi, Piero Del Boccio and Damiana Pieragostino
Int. J. Mol. Sci. 2019, 20(16), 4029; https://doi.org/10.3390/ijms20164029 - 18 Aug 2019
Cited by 56 | Viewed by 6512
Abstract
Primary open-angle glaucoma (POAG) represents the leading cause of irreversible blindness worldwide and is a multifactorial, chronic neurodegenerative disease characterized by retinal ganglion cell and visual field loss. There are many factors that are associated with the risk of developing POAG, with increased [...] Read more.
Primary open-angle glaucoma (POAG) represents the leading cause of irreversible blindness worldwide and is a multifactorial, chronic neurodegenerative disease characterized by retinal ganglion cell and visual field loss. There are many factors that are associated with the risk of developing POAG, with increased intraocular pressure being one of the most prevalent. Due to the asymptomatic nature of the disease, the diagnosis of POAG often occurs too late, which necessitates development of new effective screening strategies for early diagnosis of the disease. However, this task still remains unfulfilled. In order to provide further insights into the pathophysiology of POAG, we applied a targeted metabolomics strategy based on a high-throughput screening method for the determination of tear amino acids, free carnitine, acylcarnitines, succinylacetone, nucleosides, and lysophospholipids in naïve to therapy glaucomatous patients and normal controls. Also, we conducted proteomic analyses of the whole lacrimal fluid and purified extracellular vesicles obtained from POAG patients and healthy subjects. This multi-omics approach allowed us to conclude that POAG patients had lower levels of certain tear amino acids and lysophospholipids compared with controls. These targeted analyses also highlighted the low amount of acetylcarnitine (C2) in POAG patient which correlated well with proteomics data. Moreover, POAG tear proteins seemed to derive from extracellular vesicles, which carried a specific pro-inflammatory protein cargo. Full article
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17 pages, 2724 KiB  
Article
Ocular-Component-Specific miRNA Expression in a Murine Model of Lens-Induced Myopia
by Yasuhisa Tanaka, Toshihide Kurihara, Yumi Hagiwara, Shin-ichi Ikeda, Kiwako Mori, Xiaoyan Jiang, Hidemasa Torii and Kazuo Tsubota
Int. J. Mol. Sci. 2019, 20(15), 3629; https://doi.org/10.3390/ijms20153629 - 24 Jul 2019
Cited by 20 | Viewed by 3610
Abstract
To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA [...] Read more.
To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation. Full article
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14 pages, 4366 KiB  
Article
Transcriptome Analysis Did Not Show Endogenous Stem Cell Characteristics in Murine Lgr5+ Retinal Cells
by Carolyn Trepp, Ana Maria Quintela Pousa and Volker Enzmann
Int. J. Mol. Sci. 2019, 20(14), 3547; https://doi.org/10.3390/ijms20143547 - 19 Jul 2019
Cited by 1 | Viewed by 2918
Abstract
Lgr5, an intestinal adult stem cell marker, was recently also found in neuronal tissues. We investigated whether retinal Lgr5+ cells express properties of neural stem cells (NSC) and/or of differentiated interneurons during retinal development. RNA was isolated from Lgr5+ and Lgr5 [...] Read more.
Lgr5, an intestinal adult stem cell marker, was recently also found in neuronal tissues. We investigated whether retinal Lgr5+ cells express properties of neural stem cells (NSC) and/or of differentiated interneurons during retinal development. RNA was isolated from Lgr5+ and Lgr5 populations from postnatal day 5 (PN5) and adult retinas of Lgr5EGFP-Ires-CreERT2 knock-in mice sorted by fluorescence-activated cell sorting (FACS). Transcriptome analyses were performed on two RNA samples of each developmental stage (PN5 and adult). The online platform PANTHER (Protein ANalysis THrough Evolutionary Relationships) was used to determine overrepresented gene ontology (GO) terms of biological processes within the set of differentially expressed genes. The detailed evaluation included gene expression in regard to stem cell maintenance/proliferation, cell cycle, and Wnt signaling but also markers of differentiated retinal neurons. None of the enriched GO terms of upregulated genes of Lgr5+ cells showed a positive association to NSC. On the contrary, NSC maintenance and proliferation rather prevail in the Lgr5 cell population. Furthermore, results suggesting that Wnt signaling is not active in the Lgr5+ population. Therefore, our transcriptome analysis of Lgr5+ retinal cells suggest that these cells are differentiated neurons, specifically glycinergic amacrine cells. Full article
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19 pages, 5320 KiB  
Article
A Novel HIF Inhibitor Halofuginone Prevents Neurodegeneration in a Murine Model of Retinal Ischemia-Reperfusion
by Hiromitsu Kunimi, Yukihiro Miwa, Hiroyoshi Inoue, Kazuo Tsubota and Toshihide Kurihara
Int. J. Mol. Sci. 2019, 20(13), 3171; https://doi.org/10.3390/ijms20133171 - 28 Jun 2019
Cited by 25 | Viewed by 4769
Abstract
Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we [...] Read more.
Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases. Full article
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17 pages, 4045 KiB  
Article
Tear Proteomics Approach to Monitoring Sjögren Syndrome or Dry Eye Disease
by Ming-Tse Kuo, Po-Chiung Fang, Tsai-Ling Chao, Alexander Chen, Yu-Hsuan Lai, Yu-Ting Huang and Chia-Yi Tseng
Int. J. Mol. Sci. 2019, 20(8), 1932; https://doi.org/10.3390/ijms20081932 - 19 Apr 2019
Cited by 43 | Viewed by 4364
Abstract
Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components [...] Read more.
Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components to allow for SS-DED monitoring and avoid stably controlled SS-DED patients from re-entering a vicious cycle. This prospective case-control study compared stable SS-DED patients with non-SS-DED control from several aspects, including clinical indices for TF homeostasis, 2 DED diagnostic biomarkers (MMP-9 and lactoferrin), and the proteome of flush tears. Compared with non-SS-DED controls, stably controlled SS-DED subjects had less tear secretion and higher ocular surface inflammation, a higher concentration ratio of tear MMP-9/lactoferrin, a more diverse tear proteome, and lower spectral intensities of lipocalin-1, lacritin, and prolactin-inducible protein among the abundant tear proteins. For stable SS-DED patients, the concentration ratio of tear MMP-9/lactoferrin and the corrected lipocalin-1 signal was positively correlated with ocular inflammation and TF stability, respectively. MMP-9 released from stressed ocular surface epithelium and lipocalin-1 secreted from the energetic lacrimal gland are two tear biomarkers responding well to TF homeostasis. The tear proteomics approach through flush tears is a promising method for monitoring SS-DED patients with a standardized sampling procedure and lactoferrin-corrected analysis. Full article
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Review

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34 pages, 1061 KiB  
Review
Functional Genomics of the Retina to Elucidate its Construction and Deconstruction
by Frédéric Blond and Thierry Léveillard
Int. J. Mol. Sci. 2019, 20(19), 4922; https://doi.org/10.3390/ijms20194922 - 04 Oct 2019
Cited by 5 | Viewed by 3743
Abstract
The retina is the light sensitive part of the eye and nervous tissue that have been used extensively to characterize the function of the central nervous system. The retina has a central position both in fundamental biology and in the physiopathology of neurodegenerative [...] Read more.
The retina is the light sensitive part of the eye and nervous tissue that have been used extensively to characterize the function of the central nervous system. The retina has a central position both in fundamental biology and in the physiopathology of neurodegenerative diseases. We address the contribution of functional genomics to the understanding of retinal biology by reviewing key events in their historical perspective as an introduction to major findings that were obtained through the study of the retina using genomics, transcriptomics and proteomics. We illustrate our purpose by showing that most of the genes of interest for retinal development and those involved in inherited retinal degenerations have a restricted expression to the retina and most particularly to photoreceptors cells. We show that the exponential growth of data generated by functional genomics is a future challenge not only in terms of storage but also in terms of accessibility to the scientific community of retinal biologists in the future. Finally, we emphasize on novel perspectives that emerge from the development of redox-proteomics, the new frontier in retinal biology. Full article
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17 pages, 1126 KiB  
Review
Prospective Application of Activity-Based Proteomic Profiling in Vision Research-Potential Unique Insights into Ocular Protease Biology and Pathology
by Hui Peng and John D. Hulleman
Int. J. Mol. Sci. 2019, 20(16), 3855; https://doi.org/10.3390/ijms20163855 - 08 Aug 2019
Cited by 2 | Viewed by 3140
Abstract
Activity-based proteomic profiling (ABPP) is a powerful tool to specifically target and measure the activity of a family of enzymes with the same function and reactivity, which provides a significant advantage over conventional proteomic strategies that simply provide abundance information. A number of [...] Read more.
Activity-based proteomic profiling (ABPP) is a powerful tool to specifically target and measure the activity of a family of enzymes with the same function and reactivity, which provides a significant advantage over conventional proteomic strategies that simply provide abundance information. A number of inherited and age-related eye diseases are caused by polymorphisms/mutations or abnormal expression of proteases including serine proteases, cysteine proteases, and matrix metalloproteinases, amongst others. However, neither conventional genomic, transcriptomic, nor traditional proteomic profiling directly interrogate protease activities. Thus, leveraging ABPP to probe the activity of these enzyme classes as they relate to normal function and pathophysiology of the eye represents a unique potential opportunity for disease interrogation and possibly intervention. Full article
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14 pages, 552 KiB  
Review
An Omics Approach to Diagnosing or Investigating Fungal Keratitis
by Ming-Tse Kuo, Jiunn-Liang Chen, Shiuh-Liang Hsu, Alexander Chen and Huey-Ling You
Int. J. Mol. Sci. 2019, 20(15), 3631; https://doi.org/10.3390/ijms20153631 - 25 Jul 2019
Cited by 24 | Viewed by 10029
Abstract
Fungal keratitis (FK) is one of the most severe corneal infectious diseases. FK often leads to poor visual prognosis and thus requires accurate diagnosis. Conventional approaches, including clinical diagnoses, smears, and cultures, often fail to provide reliable diagnostic value. Omics approaches, such as [...] Read more.
Fungal keratitis (FK) is one of the most severe corneal infectious diseases. FK often leads to poor visual prognosis and thus requires accurate diagnosis. Conventional approaches, including clinical diagnoses, smears, and cultures, often fail to provide reliable diagnostic value. Omics approaches, such as those using genomic, metagenomic, and tear proteomic data sources, provide promising features for improving the diagnosis and monitoring the progression of FK. Genomic approaches are based mainly on detecting amplicons of ribosomal RNA genes, and internal transcribed spacers are gradually gaining popularity in clinical practices. A metagenomic approach based on 16S rRNA genes may help monitor the dynamic change of conjunctival microbiota associated with an FK event, whereas that based on shot-gun and 18S rRNA target enrichment sequencing could have the potential to diagnose FK using clinical samples. A tear proteomic approach may provide comprehensive information about ocular surface defense and injury during FK. Representative up- and down-regulated proteins during FK could also be used as biomarkers to determine the clinical course and develop a treatment strategy in different stages of FK. Consequently, a personalized tear proteomic approach will soon play a key role in FK management. Full article
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19 pages, 1895 KiB  
Review
Dyslipidemia and Meibomian Gland Dysfunction: Utility of Lipidomics and Experimental Prospects with a Diet-Induced Obesity Mouse Model
by Eugene A. Osae, Philipp Steven, Rachel Redfern, Samuel Hanlon, C. Wayne Smith, Rolando E. Rumbaut and Alan R. Burns
Int. J. Mol. Sci. 2019, 20(14), 3505; https://doi.org/10.3390/ijms20143505 - 17 Jul 2019
Cited by 24 | Viewed by 7819
Abstract
Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and loss of ocular surface homeostasis. Increasingly, several observational clinical studies suggest that dyslipidemia (elevated blood cholesterol, triglyceride or lipoprotein levels) can initiate the development of MGD. However, conclusive evidence is [...] Read more.
Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and loss of ocular surface homeostasis. Increasingly, several observational clinical studies suggest that dyslipidemia (elevated blood cholesterol, triglyceride or lipoprotein levels) can initiate the development of MGD. However, conclusive evidence is lacking, and an experimental approach using a suitable model is necessary to interrogate the relationship between dyslipidemia and MGD. This systematic review discusses current knowledge on the associations between dyslipidemia and MGD. We briefly introduce a diet-induced obesity model where mice develop dyslipidemia, which can serve as a potential tool for investigating the effects of dyslipidemia on the meibomian gland. Finally, the utility of lipidomics to examine the link between dyslipidemia and MGD is considered. Full article
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