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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 -
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 -
International Ophthalmology May 2024There is limited literature on the ocular manifestations in patients with psoriasis. Therefore, this study aimed to identify the prevalence of and factors associated...
PURPOSE
There is limited literature on the ocular manifestations in patients with psoriasis. Therefore, this study aimed to identify the prevalence of and factors associated with ocular manifestations in adults with psoriasis.
METHODS
This cross-sectional study included Brazilian adults with psoriasis. The dermatological evaluation included diagnosis, clinical form, Psoriasis Area and Severity Index (PASI) measurement, and location of the lesions. Patients underwent a full ophthalmological examination, including the Schirmer I test, Rose Bengala staining, and tear breakup time tests. The results were analyzed using chi-square and Pearson's linear correlation tests.
RESULTS
Of the 130 patients assessed, 118 (90.8%) exhibited ocular abnormalities, with meibomian gland dysfunction (MGD) being the most prevalent (59.2%), followed by dry eye disease (DED) (56.2%). A significant correlation was observed between MGD and PASI (p = 0.05), and between MGD and certain treatment modalities. DED was significantly associated with PASI (p < 0.05). Concurrent use of acitretin was identified as an independent predictor of MGD (odds ratio [OR] = 3.5, p < 0.05), whereas PASI was a protective factor against DED (OR = 0.39, p < 0.01).
CONCLUSION
Given the high prevalence of eye disease among individuals with psoriasis, routine ophthalmological assessments are recommended to prevent possible ocular complications.
Topics: Humans; Cross-Sectional Studies; Male; Psoriasis; Female; Brazil; Adult; Middle Aged; Prevalence; Dry Eye Syndromes; Meibomian Gland Dysfunction; Severity of Illness Index; Aged; Young Adult
PubMed: 38705919
DOI: 10.1007/s10792-024-03147-0 -
Annals of Anatomy = Anatomischer... May 2024The ocular system is in constant interaction with the environment and with numerous pathogens. The ATP-binding cassette (ABC) transporters represent one of the largest...
The ocular system is in constant interaction with the environment and with numerous pathogens. The ATP-binding cassette (ABC) transporters represent one of the largest groups among the transmembrane proteins. Their relevance has been demonstrated for their defense function against biotic and abiotic stress factors, for metabolic processes in tumors and for their importance in the development of resistance to drugs. The aim of this study was to analyze which ABC transporters are expressed at the ocular surface and in the human lacrimal apparatus. Using RT-PCR, all ABC transporters known to date in humans were examined in tissue samples from human cornea, conjunctiva, meibomian glands and lacrimal glands. The RT-PCR analyses revealed the presence of all ABC transporters in the samples examined, although the results for some of the 48 transporters known in human and analyzed were different in the various tissues. The present results provide information on the expression of ABC transporters at the mRNA level on the ocular surface and in the lacrimal system. Their detection forms the basis for follow-up studies at the protein level, which will provide more information about their physiological significance at the ocular surface and in the lacrimal system and which may explain pathological effects such as drug resistance.
PubMed: 38697581
DOI: 10.1016/j.aanat.2024.152272 -
Investigative Ophthalmology & Visual... Apr 2024The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively...
PURPOSE
The lacrimal gland (LG) is the main organ responsible for tear secretion and an important pathogenic site for dry eye disease (DED). This study aimed to comprehensively characterize LG cellular heterogeneity under normal and DED conditions using single-nucleus RNA sequencing (snRNA-seq).
METHODS
Single LG nuclei isolated from mice with or without DED induced by scopolamine (SCOP)/desiccating stress (DS) were subjected to snRNA-seq using the 10x Genomics platform. These cells were clustered and annotated using the t-distributed stochastic neighbor embedding (t-SNE) method and unbiased computational informatic analysis. Cluster identification and functional analysis were performed based on marker gene expression and bioinformatic data mining.
RESULTS
The snRNA-seq analysis of 30,351 nuclei identified eight major cell types, with acinar cells (∼72.6%) being the most abundant cell type in the LG. Subclustering analysis revealed that the LG mainly contained two acinar cell subtypes, two ductal cell subclusters, three myoepithelial cell (MECs) subtypes, and four immunocyte subclusters. In the SCOP-induced DED model, three major LG parenchymal cell types were significantly altered, characterized by a reduced proportion of acinar cells with a lowered secretion potential and an augmented proportion of ductal cells and MECs. LG immunocytes in DED scenarios showed an intensified inflammatory response and dysregulated intercellular communication with three major LG parenchymal cells.
CONCLUSIONS
Overall, this study offers a systemic single-nucleus transcriptomic profile of LGs in both normal and DED conditions and an atlas of the complicated interactions of immunocytes with major LG parenchymal cells. The findings also facilitate understanding the pathogenesis of DED.
Topics: Animals; Dry Eye Syndromes; Mice; Scopolamine; Lacrimal Apparatus; Disease Models, Animal; Mice, Inbred C57BL; Female; Cell Nucleus; Tears; Epithelial Cells
PubMed: 38687491
DOI: 10.1167/iovs.65.4.46 -
Journal of Personalized Medicine Mar 2024Anti-glaucoma eye drops have been investigated due to their production of fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal...
BACKGROUND
Anti-glaucoma eye drops have been investigated due to their production of fibrotic changes on the conjunctival surface, undermining the functioning of the upper lacrimal drainage system. We aimed to assess whether these effects may impair the effectiveness of endoscopic endonasal dacryocystorhinostomy (EE-DCR).
METHODS
This is a single-center observational retrospective study on EE-DCR via a posterior approach. Resolution of epiphora and dacryocystitis were analyzed after 1 (T1) and 6-months (T2) from surgery. Surgical success was defined as anatomical (patency at irrigation, no recurring dacryocystitis) or complete (zeroing of Munk score).
RESULTS
Twenty patients (32 sides) were enrolled. Preoperatively, 93.75% ( = 30/32) presented severe (Munk 3-4) epiphora and 68.75% ( = 22/32) recurrent dacryocystitis. At T1, 50.0% ( = 16/32) were referred with residual epiphora (Munk ≥ 1) and 18.75% ( = 6/32) dacryocystitis. At T2, 31.25% ( = 10/32) still complained of epiphora (Munk ≥ 1) and 6.25% ( = 2/32) dacryocystitis. Difference of outcomes at aggregate and paired timepoints (except for T1 versus T2) resulted in statistical significance ( < 0.05). At T2, 22 (68.75%) complete, 8 (25.0%) anatomical successes and 2 (6.25%) surgical failures were observed.
CONCLUSIONS
Despite the chronic uptake of anti-glaucoma eye drops, EE-DCR guaranteed high rates of clinical relief from epiphora and remarkable decreases in the rates of recurrent dacryocystitis.
PubMed: 38672975
DOI: 10.3390/jpm14040348 -
Arquivos Brasileiros de Oftalmologia 2024The purpose of this study is to assess the long-term outcomes of modified transcanalicular diode laser dacryocystorhinostomy in a large cohort of patients affected by...
PURPOSE
The purpose of this study is to assess the long-term outcomes of modified transcanalicular diode laser dacryocystorhinostomy in a large cohort of patients affected by primary acquired nasolacrimal duct obstruction.
METHODS
This study, conducted from January 17 to June 2022, encompassed 141 patients (159 procedures) who underwent modified transcanalicular diode laser dacryocystorhinostomy (MT-DCR). The procedure employed an 810-nm diode laser. Patients were monitored for at least a year after the intervention. Anatomical success was determined by ostium patency upon irrigation, while functional success referred to epiphora resolution. Parameters studied included patient demographics, procedure duration, complications, and both anatomical and functional success. Statistical analysis was performed using the Statistical Package for the Social Sciences software, with results considered significant at a 95% confidence interval (p≤0.05).
RESULTS
A total of 159 lacrimal drainage systems (141 patients: 112 women and 29 men) were included in this study. Among them, 18 underwent bilateral procedures. The average patient age was 58 years (range: 34-91 years), and the average surgical duration was 24 minutes (range: 18-35 minutes). One year after the surgery, MT-DCR exhibited anatomical and functional success rates of 84.9% (135/159) and 83% (132/159), respectively.
CONCLUSION
MT-DCR achieved an anatomical success rate of 84.9%, reflecting an excellent outcome. However, further extensive studies with larger sample sizes and longer follow-up periods are necessary to substantiate these findings.
Topics: Humans; Dacryocystorhinostomy; Female; Male; Middle Aged; Adult; Aged; Treatment Outcome; Lasers, Semiconductor; Aged, 80 and over; Lacrimal Duct Obstruction; Time Factors; Nasolacrimal Duct; Operative Time; Retrospective Studies
PubMed: 38656028
DOI: 10.5935/0004-2749.2023-0143 -
Investigative Ophthalmology & Visual... Apr 2024This study aims to elucidate the calcitonin gene-related peptide (CGRP) mediation and primary mechanism of corneal sensory nerves on tear production of the lacrimal...
PURPOSE
This study aims to elucidate the calcitonin gene-related peptide (CGRP) mediation and primary mechanism of corneal sensory nerves on tear production of the lacrimal gland.
METHODS
Mouse corneal denervation models were constructed through surgical axotomy, pharmacologic treatment with capsaicin or resiniferatoxin, and Trpv1-Cre/DTR mice with diphtheria toxin injection. The capsaicin-treated mice received subconjunctival injection of CGRP or substance P, while the normal C57BL/6J mice were administered with CGRP receptor antagonist BIBN-4096. Furthermore, double immunostaining of c-FOS+ and choline acetyltransferase was used to evaluate the activation of the superior salivatory nucleus (SSN). Mouse lacrimal glands were collected for transcriptomic sequencing and subsequent RNA and protein expression analysis.
RESULTS
The corneal denervated mice exhibited a significant reduction in corneal sensitivity and tear secretion. In capsaicin-treated mice, tear secretion decreased to 2.5 ± 0.5 mm compared to 6.3 ± 0.9 mm in control mice (P < 0.0001). However, exogenous administration of CGRP in capsaicin-treated mice increased tear secretion from 2.6 ± 0.5 mm to 4.5 ± 0.5 mm (P = 0.0009), while BIBN-4096 treatment reduced tear secretion to 3.4 ± 0.5 mm when compared to 7.3 ± 0.7 mm in control mice (P = 0.0022). Furthermore, c-FOS+ cell number in the SSN increased by twofold (P = 0.0168) after CGRP administration compared with capsaicin-treated mice. In addition, the expressions of CCNA2, Ki67, PCNA, and CDK1 in acinar cells of the lacrimal gland were impaired by corneal denervation and alleviated by CGRP administration.
CONCLUSIONS
CGRP released by corneal sensory nerves mediates tear secretion of the lacrimal gland, providing a new strategy for improving tear secretion in patients with neurotrophic keratitis.
Topics: Animals; Mice; Calcitonin Gene-Related Peptide; Capsaicin; Genes, fos; Lacrimal Apparatus; Mice, Inbred C57BL; Proto-Oncogene Proteins c-fos
PubMed: 38635244
DOI: 10.1167/iovs.65.4.30 -
Scientific Reports Apr 2024To analyze the clinical characteristics of mucinous obstruction diagnosed by dacryoendoscopy and compared the cytological changes with membranous obstruction using a...
To analyze the clinical characteristics of mucinous obstruction diagnosed by dacryoendoscopy and compared the cytological changes with membranous obstruction using a modified liquid-based thin prep cytology method. A retrospective chart review was conducted on 53 eyes of 51 patients with mucus obstruction based on dacryoendoscopic findings from January 2022 to October 2022. Liquid-based thin-prep cytology was performed by irrigating the inside of the nasolacrimal drainage system with saline during dacryoendoscopy-guided silicone tube intubation. Pathological findings were analyzed through a comparison of mucinous obstruction with membranous obstruction as determined by dacryoendoscopic findings. The modified liquid-based thin prep cytology technique had a higher cytology detection rate across all cases. Mucinous obstruction exhibited a significantly higher number of successful canalicular irrigation test cases compared to membranous obstruction. In mucinous obstruction, epithelial squamous cells were more frequently detected in pre-sac obstruction, whereas columnar epithelial cells were predominant in post-sac obstruction. Inflammatory cells showed a stronger correlation with primary change and post-sac obstruction. Bacterial colonies were observed exclusively in cases of mucinous obstruction. The use of a modified liquid-based thin prep cytology method enables the examination of histopathological changes in the lacrimal passage in primary acquired nasolacrimal duct obstruction (PANDO), particularly in cases of mucinous obstruction, without the need for invasive biopsies. These findings enhance the understanding of the etiopathogenesis of mucinous obstruction, complementing knowledge of membranous obstruction in PANDO.
Topics: Humans; Nasolacrimal Duct; Dacryocystorhinostomy; Lacrimal Duct Obstruction; Retrospective Studies; Endoscopy
PubMed: 38632478
DOI: 10.1038/s41598-024-59580-9