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Indian Journal of Ophthalmology Apr 2023To understand the bacterial microbiome changes associated with Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS) aqueous-deficient dry eyes compared to healthy...
PURPOSE
To understand the bacterial microbiome changes associated with Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS) aqueous-deficient dry eyes compared to healthy eyes.
METHODS
Bacterial microbiome was generated from the deoxyribonucleic acid of tear film samples in healthy (n = 33), SS (n = 17), and NSS (n = 28) individuals. Sequencing of the V3-V4 region of the 16S rRNA gene was performed on the Illumina HiSeq2500 platform. Quantitative Insights Into Microbial Ecology (QIIME) pipeline was used to assign taxa to sequences. Statistical analysis was performed in R to assess the alpha diversity and beta diversity indices. Significant changes between the healthy, SS, and NSS cohorts were depicted by principal coordinate analysis (PCoA), differential abundance, and network analysis.
RESULTS
Tear microbiome was generated in healthy, SS, and NSS samples. Phyla Actinobacteria, Firmicutes, and Bacteroidetes showed significant changes in SS and NSS compared to healthy. Genera Lactobacillus and Bacillus were predominantly present in all samples. PCoA and heat map analysis showed distinct clusters for SS and NSS from the healthy cohort. Genera Prevotella, Coriobacteriaceae UCG-003, Enterococcus, Streptomyces, Rhodobacter, Ezakiella, and Microbacterium significantly increased in abundance in SS and NSS compared to a healthy cohort. Bacteria-bacteria interaction in SS, NSS, and healthy cohorts was predicted by CoNet network analysis. This analysis predicted a major hub of interaction for the pro-inflammatory bacterium Prevotella in the SS and NSS cohorts.
CONCLUSION
The results of the study indicate significant changes in the phyla and genera in SS and NSS compared to healthy. Both discriminative analysis and network analysis indicated a possible association of predominant pro-inflammatory bacteria with SS and NSS.
Topics: Humans; RNA, Ribosomal, 16S; Dry Eye Syndromes; Sjogren's Syndrome; Tears; Microbiota; Bacteria
PubMed: 37026303
DOI: 10.4103/IJO.IJO_2821_22 -
Indian Journal of Ophthalmology Apr 2023Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous-deficient dry eye (ADDE), a subtype of DED, is characterized by... (Review)
Review
Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous-deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one-third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long-term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well-being of affected individuals. This review discusses the various etiologies of ADDE, highlights a pathophysiology-based approach for evaluating underlying contributors, outlines various diagnostic tests, and reviews treatment options. We present the current standards and discuss ongoing research in this field. Through this review, we propose a treatment algorithm that would be useful for an ophthalmologist in diagnosing and managing individuals with ADDE.
Topics: Humans; Quality of Life; Tears; Dry Eye Syndromes; Eye
PubMed: 37026265
DOI: 10.4103/IJO.IJO_2808_22 -
Mediators of Inflammation 2018Dry eye disease (DED) is the most common ocular disease and affects millions of individuals worldwide. DED encompasses a heterogeneous group of diseases that can be... (Review)
Review
Dry eye disease (DED) is the most common ocular disease and affects millions of individuals worldwide. DED encompasses a heterogeneous group of diseases that can be generally divided into two forms including aqueous-deficient and evaporative DED. Evidence suggests that these conditions arise from either failure of lacrimal gland secretion or low tear film quality. In its secondary form, DED is often associated with autoimmune diseases such as Sjögren's syndrome and rheumatoid arthritis. Current treatment strategies for DED are limited to anti-inflammatory medications that target the immune system as the source of deleterious inflammation and tissue injury. However, there is a lack of understanding of the underlying pathogenesis of DED, and subsequently, there are very few effective treatment strategies. The gap in our knowledge of the etiology of primary DED is in part because the majority of research in DED focused on secondary autoimmune causes. This review focuses on what is currently understood about the contribution of innate and adaptive immune cell populations in the pathogenesis of DED and highlights the need to continue investigating the central role of immunity driving DED.
Topics: Anti-Inflammatory Agents; CD4-Positive T-Lymphocytes; Dry Eye Syndromes; Humans; Immunity, Innate; Inflammation; Killer Cells, Natural; Neutrophils
PubMed: 30158831
DOI: 10.1155/2018/2532314 -
Experimental Eye Research Dec 2023Sjogren's syndrome (SS) is a chronic autoimmune disorder that affects exocrine glands, particularly lacrimal glands, leading to dry eye disease (DED). DED is a common... (Review)
Review
Sjogren's syndrome (SS) is a chronic autoimmune disorder that affects exocrine glands, particularly lacrimal glands, leading to dry eye disease (DED). DED is a common ocular surface disease that affects millions of people worldwide, causing discomfort, visual impairment, and even blindness in severe cases. However, there is no definitive cure for DED, and existing treatments primarily relieve symptoms. Consequently, there is an urgent need for innovative therapeutic strategies based on the pathophysiology of DED. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool for various autoimmune disorders, including SS-related DED (SS-DED). A particularly intriguing facet of MSCs is their ability to produce extracellular vesicles (EVs), which contain various bioactive components such as proteins, lipids, and nucleic acids. These molecules play a key role in facilitating communication between cells and modulating a wide range of biological processes. Importantly, MSC-derived EVs (MSC-EVs) have therapeutic properties similar to those of their parent cells, including immunomodulatory, anti-inflammatory, and regenerative properties. In addition, MSC-EVs offer several notable advantages over intact MSCs, including lower immunogenicity, reduced risk of tumorigenicity, and greater convenience in terms of storage and transport. In this review, we elucidate the underlying mechanisms of SS-DED and discuss the relevant mechanisms and targets of MSC-EVs in treating SS-DED. In addition, we comprehensively review the broader landscape of EV application in autoimmune and corneal diseases. This review focuses on the efficacy of MSC-EVs in treating SS-DED, a field of study that holds considerable appeal due to its multifaceted regulation of immune responses and regenerative functions.
Topics: Humans; Sjogren's Syndrome; Dry Eye Syndromes; Autoimmune Diseases; Extracellular Vesicles; Mesenchymal Stem Cells
PubMed: 37951337
DOI: 10.1016/j.exer.2023.109716 -
Indian Journal of Ophthalmology Apr 2023The incidence of dry eye disease has increased manifold in the past few years with more patients presenting with these complaints to our clinics every day. In the more...
The incidence of dry eye disease has increased manifold in the past few years with more patients presenting with these complaints to our clinics every day. In the more severe forms of disease, it is important to evaluate for any systemic association which could be driving the disease such as in Sjogren's syndrome. Understanding the possible varied etiopathogenesis and knowing when to evaluate, form an important part of treating this condition effectively. In addition, it is sometimes confusing as to which investigations to order and how to prognosticate the disease in these situations. This article simplifies this into an algorithmic approach with insights from the ocular and systemic point of view.
Topics: Humans; Dry Eye Syndromes; Sjogren's Syndrome
PubMed: 37026264
DOI: 10.4103/IJO.IJO_3003_22 -
International Journal of Molecular... Jan 2023Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye...
Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study aimed to illustrate the effects of mesenchymal stem cells on the attenuation of dry eyes (DE) through the inhibition of autophagy markers in a SS mouse model. NOD/ShiLtJ female mice with developed DE were treated with either subconjunctival or lacrimal gland injections of hMSCs (Catholic MASTER Cells). After maintenance for 14 days, clinical DE markers such as tear secretion and corneal staining were observed, as well as goblet cell counts in the conjunctiva, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal glands. Proinflammatory cytokine expressions of the cornea and conjunctiva, as well as the lacrimal glands, were examined. Clinical markers, such as tear secretion and corneal stain scores, goblet cell counts in the conjunctiva, and foci infiltrations in the lacrimal glands were attenuated in mice treated with subconjunctival or lacrimal gland injections of hMSCs compared to the PBS-treated control group. B cell marker B220 decreased in the lacrimal glands of hMSCs-treated mice, as well as reduced proinflammatory cytokine expressions in the lacrimal glands and cornea. Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model.
Topics: Female; Animals; Mice; Sjogren's Syndrome; Tears; Mice, Inbred NOD; Dry Eye Syndromes; Lacrimal Apparatus; Mesenchymal Stem Cells; Biomarkers; Cytokines; Disease Models, Animal
PubMed: 36674547
DOI: 10.3390/ijms24021039 -
Journal of Neuroinflammation May 2021Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient...
BACKGROUND
Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED.
METHODS
Chronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests.
RESULTS
First, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED.
CONCLUSION
These data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.
Topics: Animals; Capsaicin; Cornea; Dry Eye Syndromes; Male; Mice; Mice, Inbred C57BL; Pain; Syndrome; TRPV Cation Channels
PubMed: 33975636
DOI: 10.1186/s12974-021-02162-7 -
The British Journal of Ophthalmology Jun 1997To determine the relation between dry eye and Meige's syndrome. (Comparative Study)
Comparative Study
AIMS
To determine the relation between dry eye and Meige's syndrome.
METHODS
325 patients with dry eye were divided into those responsive to topical and other forms of treatment (n = 276) and those who were not (n = 49). A neuropsychiatric examination was performed to check for Meige's syndrome in the latter group.
RESULTS
Twenty eight (57%) of the treatment unresponsive patients were diagnosed with Meige's syndrome.
CONCLUSIONS
There is a subgroup of patients with dry eye who do not respond to simple therapy. More than half of these patients have Meige's syndrome and need psychiatric, as well as ophthalmic, care.
Topics: Adult; Aged; Dry Eye Syndromes; Female; Humans; Male; Meige Syndrome; Middle Aged; Treatment Outcome
PubMed: 9274405
DOI: 10.1136/bjo.81.6.439 -
Indian Journal of Ophthalmology Apr 2023Immunosuppression in aqueous-deficient dry eye disease (ADDE) is required not only to improve the symptoms and signs but also to prevent further progression of the... (Review)
Review
Immunosuppression in aqueous-deficient dry eye disease (ADDE) is required not only to improve the symptoms and signs but also to prevent further progression of the disease and its sight-threatening sequelae. This immunomodulation can be achieved through topical and/or systemic medications, and the choice of one drug over the other is determined by the underlying systemic disease. These immunosuppressive agents require a minimum of 6-8 weeks to achieve their beneficial effect, and during this time, the patient is usually placed on topical corticosteroids. Antimetabolites such as methotrexate, azathioprine, and mycophenolate mofetil, along with calcineurin inhibitors, are commonly used as first-line medications. The latter have a pivotal role in immunomodulation since T cells contribute significantly to the pathogenesis of ocular surface inflammation in dry eye disease. Alkylating agents are largely limited to controlling acute exacerbations with pulse doses of cyclophosphamide. Biologic agents, such as rituximab, are particularly useful in patients with refractory disease. Each group of drugs has its own side-effect profiles and requires a stringent monitoring schedule that must be followed to prevent systemic morbidity. A customized combination of topical and systemic medications is usually required to achieve adequate control, and this review aims to help the clinician choose the most appropriate modality and monitoring regimen for a given case of ADDE.
Topics: Humans; Azathioprine; Dry Eye Syndromes; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Methotrexate
PubMed: 37026249
DOI: 10.4103/IJO.IJO_2818_22 -
Acta Ophthalmologica Dec 2017To critically appraise scientific evidence regarding the efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids for the treatment of dry eye... (Review)
Review
PURPOSE
To critically appraise scientific evidence regarding the efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids for the treatment of dry eye syndrome (DES).
METHODS
A systematic review of randomized clinical trials was performed. Two independent reviewers selected and analysed the scientific papers that met inclusion and exclusion criteria. Objective and subjective efficacy outcomes were assessed.
RESULTS
The trials involved a total of 2591 patients in fifteen independent studies. All studies were published between 2005 and 2015. The supplements used were mostly omega-3 and omega-6 in different proportions. Subjective improvement was measured using mainly Ocular Surface Disease Index (OSDI) test and Dry Eye Severity Score (DESS) test: significant differences in favour of the experimental group were found in seven of the studies. The objective amelioration was assessed by lacrimal function parameters: Tear break-up time (TBUT) significantly increased in nine studies and Schirmer's test in four studies.
CONCLUSION
We observed a discrete improvement in the parameters of tear function. Scientific evidence is not strong enough to systematically recommend the use of omega-3 and omega-6 fatty acids as a standalone treatment of DES independently from its aetiology. However, they could be considered as an effective alternative to topical treatment in patients with DES secondary to certain pathologies.
Topics: Dietary Supplements; Dry Eye Syndromes; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28371493
DOI: 10.1111/aos.13428