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Experimental Biology and Medicine... 2024Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal...
Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.
Topics: Animals; Lacrimal Apparatus; Tears; Naltrexone; Rats, Sprague-Dawley; Male; Diabetes Mellitus, Experimental; Rats; Aquaporin 5; Administration, Topical; Dry Eye Syndromes
PubMed: 38756167
DOI: 10.3389/ebm.2024.10175 -
Investigative Ophthalmology & Visual... May 2024Hydrogels derived from decellularized tissues are promising biomaterials in tissue engineering, but their rapid biodegradation can hinder in vitro cultivation. This...
PURPOSE
Hydrogels derived from decellularized tissues are promising biomaterials in tissue engineering, but their rapid biodegradation can hinder in vitro cultivation. This study aimed to retard biodegradation of a hydrogel derived from porcine decellularized lacrimal glands (dLG-HG) by crosslinking with genipin to increase the mechanical stability without affecting the function and viability of lacrimal gland (LG)-associated cells.
METHODS
The effect of different genipin concentrations on dLG-HG stiffness was measured rheologically. Cell-dependent biodegradation was quantified over 10 days, and the impact on matrix metalloproteinase (MMP) activity was quantified by gelatin and collagen zymography. The viability of LG epithelial cells (EpCs), mesenchymal stem cells (MSCs), and endothelial cells (ECs) cultured on genipin-crosslinked dLG-HG was assessed after 10 days, and EpC secretory activity was analyzed by β-hexosaminidase assay.
RESULTS
The 0.5-mM genipin increased the stiffness of dLG-HG by about 46%, and concentrations > 0.25 mM caused delayed cell-dependent biodegradation and reduced MMP activity. The viability of EpCs, MSCs, and ECs was not affected by genipin concentrations of up to 0.5 mM after 10 days. Moreover, up to 0.5-mM genipin did not negatively affect EpC secretory activity compared to control groups.
CONCLUSIONS
A concentration of 0.5-mM genipin increased dLG-HG stiffness, and 0.25-mM genipin was sufficient to prevent MMP-dependent degradation. Importantly, concentrations of up to 0.5-mM genipin did not compromise the viability of LG-associated cells or the secretory activity of EpCs. Thus, crosslinking with genipin improves the properties of dLG-HG for use as a substrate in LG tissue engineering.
Topics: Animals; Iridoids; Swine; Hydrogels; Tissue Engineering; Cross-Linking Reagents; Cell Survival; Cells, Cultured; Mesenchymal Stem Cells; Epithelial Cells; Endothelial Cells; Biocompatible Materials
PubMed: 38748430
DOI: 10.1167/iovs.65.5.24 -
Acta Otorhinolaryngologica Italica :... May 2024
Review
Topics: Humans; Eye Neoplasms; Endoscopy; Lacrimal Apparatus; Lacrimal Apparatus Diseases
PubMed: 38745518
DOI: 10.14639/0392-100X-suppl.1-44-2024-N2966 -
Radiology Case Reports Aug 2024Sarcoidosis, a multifaceted granulomatous disease primarily affecting the lungs, occasionally presents in atypical locations. Lacrimal gland involvement, though rare,...
Sarcoidosis, a multifaceted granulomatous disease primarily affecting the lungs, occasionally presents in atypical locations. Lacrimal gland involvement, though rare, poses distinct diagnostic challenges. This case report details a 52-year-old female with bilateral lacrimal gland swelling initially suggestive of metastatic tumor due to a history of breast cancer. Subsequent investigations, including CT and MRI, unveiled pulmonary sarcoidosis. Discussion emphasizes the diverse ocular manifestations of sarcoidosis, with lacrimal gland participation potentially indicating early stages. Diagnostic complexities involve differentiation from other lacrimal pathologies, including neoplasms, lymphoproliferative disorders, Sjögren's syndrome, Wegener's granulomatosis, tuberculosis, and IgG4-related disease. In summary, while lacrimal gland involvement in sarcoidosis is infrequent, it should be considered in orbital masses, necessitating a comprehensive approach for accurate diagnostic orientation in such cases.
PubMed: 38737175
DOI: 10.1016/j.radcr.2024.04.010 -
International Journal of Molecular... May 2024Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix... (Review)
Review
Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix (ECM) destruction within the salivary and lacrimal glands, followed by immune cell infiltration. In this review, we have assessed the current understanding of epithelial-mesenchymal transition (EMT)-associated changes within the salivary epithelium potentially involved in salivary dysfunction and SjD pathogenesis. We performed a PubMed literature review pertaining to the determination of pathogenic events that lead to EMT-related epithelial dysfunction and signaling in SjD. Molecular patterns of epithelial dysfunction in SjD salivary glands share commonalities with EMT mediating wound healing. Pathological changes altering salivary gland integrity and function may precede direct immune involvement while perpetuating MMP9-mediated ECM destruction, inflammatory mediator expression, and eventual immune cell infiltration. Dysregulation of EMT-associated factors is present in the salivary epithelium of SjD and may be significant in initiating and perpetuating the disease. In this review, we further highlight the gap regarding mechanisms that drive epithelial dysfunction in salivary glands in the early or subclinical pre-lymphocytic infiltration stages of SjD.
Topics: Humans; Sjogren's Syndrome; Epithelial-Mesenchymal Transition; Salivary Glands; Animals; Epithelium; Epithelial Cells; Signal Transduction; Extracellular Matrix
PubMed: 38732189
DOI: 10.3390/ijms25094973 -
Contact Lens & Anterior Eye : the... May 2024Diabetes mellitus (DM) can be defined as a metabolic disorder that results from either the inability of insulin to perform its normal functions or decreased insulin...
BACKGROUND
Diabetes mellitus (DM) can be defined as a metabolic disorder that results from either the inability of insulin to perform its normal functions or decreased insulin secretion. Dry eye disease is a complex ailment of the tear film resulting in discomfort characterised by pain, a feeling of heavy eyes, grittiness, burning, dryness, itchiness, foreign body sensation, and visual disturbances. Patients with chronic conditions, i.e. DM, are more susceptible to developing dry eye due to various complications that may arise, such as, peripheral neuropathy, inflammatory alterations and reduced lacrimal gland function.
AIM
To identify the prevalence of dry eye syndrome in paediatric patients diagnosed with Diabetes Mellitus (Type 1/2).
METHOD
37 children with diabetes and 40 healthy, age group matched controls were enrolled in this study. Participants underwent a complete dry eye assessment in the following order: Ocular Surface Disease Index (OSDI) and McMonnies questionnaire, meibomian gland evaluation using white light, Tear Break-up Test (TBUT), Phenol Red Thread (PRT) test and Tear film Osmolarity test. Duration of diabetes was used as the parameter.
RESULTS
The incidence of dry eye syndrome was found to be higher among diabetics, with 15 (40.5 %) from the diabetic population compared to 4 (10.0 %) from the control group. TBUT and PRT test values were significantly reduced in children with diabetes (p < 0.001). TFO values were higher in the diabetics. No statistically significant differences were found the questionnaire scores, of the two groups, however the diabetic group appeared to be less symptomatic.
CONCLUSION
Dry eye is more common in the diabetic paediatric population. TBUT and PRT results were found to be lower in diabetics. Results showed a strong correlation between duration of diabetes and TBUT values. Healthcare practitioners, working with children diagnosed with diabetes, should raise awareness as well as encourage early dry eye screening and intervention.
CLINICAL SIGNIFICANCE
Due to the steady increase in the number of children and adolescents with diabetes, the characteristics and prevalence of dry eye syndrome in this population has become more valuable.
PubMed: 38724426
DOI: 10.1016/j.clae.2024.102175 -
PloS One 2024Branching morphogenesis is a complex process shared by many organs including the lungs, kidney, prostate, as well as several exocrine organs including the salivary,...
Branching morphogenesis is a complex process shared by many organs including the lungs, kidney, prostate, as well as several exocrine organs including the salivary, mammary and lacrimal glands. This critical developmental program ensures the expansion of an organ's surface area thereby maximizing processes of cellular secretion or absorption. It is guided by reciprocal signaling from the epithelial and mesenchymal cells. While signaling pathways driving salivary gland branching morphogenesis have been relatively well-studied, our understanding of the underlying transcriptional regulatory mechanisms directing this program, is limited. Here, we performed in vivo and ex vivo studies of the embryonic mouse submandibular gland to determine the function of the transcription factor ΔNp63, in directing branching morphogenesis. Our studies show that loss of ΔNp63 results in alterations in the differentiation program of the ductal cells which is accompanied by a dramatic reduction in branching morphogenesis that is mediated by dysregulation of WNT signaling. We show that ΔNp63 modulates WNT signaling to promote branching morphogenesis by directly regulating Sfrp1 expression. Collectively, our findings have revealed a novel role for ΔNp63 in the regulation of this critical process and offers a better understanding of the transcriptional networks involved in branching morphogenesis.
Topics: Animals; Mice; Morphogenesis; Membrane Proteins; Gene Expression Regulation, Developmental; Intercellular Signaling Peptides and Proteins; Salivary Glands; Wnt Signaling Pathway; Submandibular Gland; Trans-Activators; Cell Differentiation
PubMed: 38722977
DOI: 10.1371/journal.pone.0301082 -
International Journal of Ophthalmology 2024To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats.
AIM
To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats.
METHODS
Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (=10), and the rats fed in dry environment as the dryness group (=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins.
RESULTS
In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group.
CONCLUSION
The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.
PubMed: 38721521
DOI: 10.18240/ijo.2024.03.04 -
Integrative Medicine Research Jun 2024Tagetes erecta Linn, popularly known as Marigold, has various pharmacological effects. It is used as a dietary supplement, especially for the posterior segment of the...
BACKGROUND
Tagetes erecta Linn, popularly known as Marigold, has various pharmacological effects. It is used as a dietary supplement, especially for the posterior segment of the eye. However, the effect of T. erecta Linn on ocular disorders is still unknown. The purpose of this study was to investigate the effect of oral administration of ethanol extract of Linn flower (TE) for dry eye syndrome (DED) in a murine model.
METHODS
Twenty-four mice were subjected to desiccation stress (DS) to induce DED and subcutaneous injection of scopolamine hydrobromide was administered 4 times a day for 21 days. TE and cyclosporine A (CsA) were administered for an additional 14 days under DS conditions. Mice were randomly divided into four groups: control, TE200, TE400, and CsA. Changes in tear production and corneal fluorescein staining were measured at baseline, after 7 days of DS, and after treatment for 7 and 14 days.
RESULTS
DS significantly decreased tear production and increased corneal fluorescein score; the parameters were significantly reversed in the TE400 (oral administration of 400 mg TE/kg body weight) group. TE markedly improved DS-induced changes including corneal epithelial detachment and lacrimal gland inflammation. The anti-inflammatory effect of TE 400 supplementation was similar to that of CsA.
CONCLUSIONS
Our findings suggest that oral administration of TE may protect against DS-induced DED stabilization of the tear film and suppression of inflammation. This study provides an experimental basis for further studies on the potential clinical use of TE in preventing DED.
PubMed: 38716164
DOI: 10.1016/j.imr.2024.101038 -
Cureus Apr 2024Congenital alacrima is an uncommon condition marked by a lack of tear production that is present from birth. This condition often occurs in conjunction with various...
Congenital alacrima is an uncommon condition marked by a lack of tear production that is present from birth. This condition often occurs in conjunction with various syndromes but can also result from isolated lacrimal gland agenesis. Congenital alacrima should be evaluated in the differential diagnosis for pediatric patients presenting with symptoms of dry eyes, especially in cases without xerostomia or other systemic rheumatologic findings. Following a thorough history and examination, noninvasive imaging techniques can be utilized to assess for potential lacrimal gland agenesis and aid in confirming the diagnosis.
PubMed: 38711697
DOI: 10.7759/cureus.57732