Lacrimal osmolaritu and ocular surface in experimental model of dry eye caused by toxicity

Marques, Davi; Alves, Mônica; Módulo, Carolina Maria; Silva, Lilian Eslaine Costa Mendes da; Reinach, Peter S.; Rocha, Eduardo Melani

doi:10.5935/0034-7280.20150016

Cited by 19 publications

(21 citation statements)

References 22 publications

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“…In brief, immediately after a rising concentration of carbon dioxide resulted in death of 8- to 26-wk-old rats, ~7 by ~5-mm conjunctival specimens were excised from each eye, hemi-sectioned, positioned with the exterior surface upwards in a glass-bottom 0.75-mL recording chamber and stabilized with a harp-shaped tissue anchor (SHD26GH/10; Warner Instruments, Hamden, CT, USA). The chamber was then filled with a solution consisting of 105 mM NaCl, 15 mM NaHCO 3 , 10 Na-Hepes, 20 mM KCl, 0.5 mM CaCl 2 , 0.5 mM MgCl 2 , and 3 mM glucose; the pH was adjusted to 7.5, and a vapor pressure osmometer (Vapro 5600, Wescor, Logan, UT, USA) confirmed that osmolarity was 300 mosM, which is normosmotic for the tears of rats, rabbits, and humans [ 23 , 24 , 25 ]. Additionally of note, the K + and divalent cation concentrations, as well as the pH, reflect the values measured in normal tears of various animals and humans [ 1 , 23 , 24 , 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Bioelectric Responses of Conjunctival Goblet Cells to Dry Eye: Impact of Ion Channels on Exocytotic Function and Viability

Puro

2020

IJMS

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How ion channels impact the response of the ocular surface to dry eye is only beginning to be explored. Here, we review recent progress and provide new experimental data clarifying the exocytosis-altering actions of ion channels in conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to the pre-ocular hyperosmolarity that characterizes dry eye. Patch-clamp recordings of goblet cells located in freshly excised rat conjunctiva reveal that these mucin-releasing cells respond to sustained hyperosmolarity by sequentially activating their ATP-sensitive potassium (KATP), nonspecific cation (NSC), voltage-gated calcium (VGCC), and P2X7 channels; each of which modulates exocytosis. Based on these and other new findings, we now identify four stages in the bioelectric response of conjunctival goblet cells to extracellular hyperosmolarity. To better characterize these stages, we report that high-resolution membrane capacitance (Cm) measurements of the exocytotic activity of single goblet cells demonstrate that the replenishment of mucin-filled granules after neural-evoked exocytosis is a multi-hour process, which VGCCs markedly accelerate. Yet, we also discovered that VGCC activation is high-risk since hyperosmotic-induced goblet cell death is boosted. With dry eye treatments being far from optimal, elucidating the physiologic and pathobiologic impact of the KATP/NSC/VGCC/P2X7 pathway provides a new opportunity to identify novel therapeutic strategies.

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Section: Methodsmentioning

confidence: 99%

Bioelectric Responses of Conjunctival Goblet Cells to Dry Eye: Impact of Ion Channels on Exocytotic Function and Viability

Puro

2020

IJMS

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“…Dry eye injures the cornea in humans and companion animals; model animals of dry eye have been reported. [8][9][10] This disease reduces the quality of life in patients because it causes fatigue or pain of the eyes and eventually leads to low vision. Dry eye is known as a chronic disease associated with keratoconjunctivitis.…”

Section: Introductionmentioning

confidence: 99%

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

Hiraishi

Masum

Namba

et al. 2020

Exp Biol Med (Maywood)

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The tear film covers the cornea, and its abnormalities (including immunological) induce dry eye. Using autoimmune disease model mice, BXSB/MpJ- Yaa (BXSB-Yaa), histopathological changes in the eye and tear-secreting tissues were examined using histopathology, immunohistochemistry, and electron microscopy at 8, 20, and 28 weeks for early, middle, and late disease stages. Early and middle stage BXSB-Yaa showed increased serum autoantibody and spleen weight-to-body weight (S/B) ratio, respectively, and higher tear volume than controls, BXSB/MpJ (BXSB), at early stages, which decreased with ageing and negatively correlated with autoimmune disease indices. Smaller Meibomian gland acini, intraorbital lacrimal glands, and Harderian gland acinar cells were seen in late stage BXSB-Yaa than in BXSB; the latter two indices decreased with ageing and negatively correlated with the S/B ratio. Cell infiltration occurred in the middle stage BXSB-Yaa extraorbital lacrimal gland, and acinar cells were smaller than BXSB. The conjunctival goblet cells decreased from early to middle stages in both strains, but in BXSB-Yaa, they increased at late stages with a partial lack of microvilli on the cornea and were inversely altered with anterior epithelium thickness through ageing, suggesting that they compensated for anterior epithelium damage. In conclusion, the tear film was unstable due to an autoimmune disease condition in BXSB-Yaa. Impact statement Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjögren’s syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease.

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“…Iatrogenic dry eye associated to BAK chronic exposure has been recently recognized and is related to corneal denervation, ocular surface inflammation and corneal. [12,15].…”

Section: Introductionmentioning

confidence: 99%

Is Sjögren’s syndrome dry eye similar to dry eye caused by other etiologies? Discriminating different diseases by dry eye tests

et al. 2018

Self Cite

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PurposeDry Eye Disease (DED) is part of several conditions, including Sjögren’s syndrome (SS) and no single test to diagnosis DED. The present study intends to evaluate whether a set of signs and symptoms of DED can distinguish: a) SS from other non-overlapping systemic diseases related to DED; b) primary and secondary SS.Methods182 consecutive patients with DED were evaluated under five groups: SS, graft-versus-host disease (GVHD), Graves' orbitopathy (GO), diabetes mellitus (DM), glaucoma under treatment with benzalkonium chloride medications (BAK). Twenty-four healthy subjects were included as control group (CG). The evaluation consisted of Ocular Surface Disease Index (OSDI), Schirmer test (ST), corneal fluorescein staining (CFS) and tear film break up time (TFBUT). Indeed, a subset of DED patients (n = 130), classified as SS1, SS2 and nonSS (NSS) by the American-European Criteria were compared. Quadratic discriminant analysis (QDA) classified the individuals based on variables collected. The area under Receiver Operating Characteristics (ROC) curve evaluated the classification performance in both comparisons.ResultsComparing SS with other diseases, QDA showed that the most important variable for classification was OSDI, followed by TFBUT and CFS. Combined, these variables were able to correctly classify 62.6% of subjects in their actual group. At the discretion of the area under the ROC curve, the group with better classification was the control (97.2%), followed by DM (95.5%) and SS (92.5%). DED tests were different among the NSS, SS1 and SS2 groups. The analysis revealed that the combined tests correctly classified 54.6% of the patients in their groups. The area under the ROC curve better classified NSS (79.5%), followed by SS2 (74.4%) and SS1 (69.4%).ConclusionsDiseases that causes DED, and also SS1, SS2 and NSS are distinguishable conditions, however a single ocular tools was not able to detect the differences among the respective groups.

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Lacrimal osmolaritu and ocular surface in experimental model of dry eye caused by toxicity

Cited by 19 publications

References 22 publications

Bioelectric Responses of Conjunctival Goblet Cells to Dry Eye: Impact of Ion Channels on Exocytotic Function and Viability

Bioelectric Responses of Conjunctival Goblet Cells to Dry Eye: Impact of Ion Channels on Exocytotic Function and Viability

Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

Is Sjögren’s syndrome dry eye similar to dry eye caused by other etiologies? Discriminating different diseases by dry eye tests

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