These findings demonstrated that an ophthalmic preservative, benzalkonium chloride, induced a dry eye syndrome in rabbits with damage to the cornea and conjunctiva, decreased aqueous tear basal secretion, goblet cell loss, and MUC5AC deficiency. This rabbit model was consistent with human dry eye syndrome in both aqueous tear and mucin deficiency and may be appropriate for studying dry eye syndrome.
BackgroundDry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model.Methods and FindingsEighty white rabbits were randomly divided into four groups. One eye from each rabbit was randomly chosen to receive topical 0.1% BAC twice daily for 2 weeks (Group BAC-W2), 3 weeks (Group BAC-W3), 4 weeks (Group BAC-W4), or 5 weeks (Group BAC-W5). Fluorescein staining, Schirmer's tests, and conjunctival impression cytology were performed before BAC treatment (normal) and on days 0, 7, 14 and 21 after BAC removal. The eyeballs were collected at these time points for immunofluorescence staining, hematoxylin and eosin (HE) staining, and electron microscopy. After removing BAC, the signs of dry eye in Group BAC-W2 lasted one week. Compared with normal, there were still significant differences in the results of Schirmer's tests and fluorescein staining in Groups BAC-W3 and BAC-W4 on day 7 (P<0.05) and in Group BAC-W5 on day 14 (P<0.05). Decreases in goblet cell density remained stable in the three experimental groups at all time points (P<0.001). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21.ConclusionsA stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye).
To explore the regulation of anion secretion across rabbit corneal epithelia by extracellular ATP and to investigate the mechanism of benzalkonium chloride (BAC) induced dry eye model involved in this secretion, short circuit current and patch clamp were used. Changes in cytosolic Ca2+ concentration were measured using Fluo3. The cornea responded to apical application of ATP in short circuit current (Isc). Ion substitution experiments showed the rise in Isc due to Cl‐ and HCO3‐ secretion. Pretreatment with Cl‐ channel blockers, such as DIDS, NPPB and DPC attenuated the response. Moreover, the Isc was inhibited by U73122 and BAPTA/AM, indicating the requirement of PLC and intracellular calcium (Ca2+i) in the anion secretion. In whole‐cell patch clamp study, ATP stimulated a Ca2+‐activate Cl‐ channel and this current showed an outward rectifying I‐V relationship. In BAC‐pretreated epithelial cell, the whole‐cell current was suppressed. Dynamic changes of Ca2+i demonstrated the elevations of Ca2+i was smaller in BAC‐treated epithelia compared to control cells when they were challenged by ATP and Thapsigagin. These findings suggested ATP could induce anion secretion, and this secretion was inhibited in BAC‐evoked rabbit dry eye model. Abnormality of intracellular Ca2+ and Ca2+ activated Cl‐ channel may take charge of inhibitory anion secretion in the rabbit corneal epithelial cells of dry eye model.
Background: Dry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model.Methods and Findings: Eighty white rabbits were randomly divided into four groups. One eye from each rabbit was randomly chosen to receive topical 0.1% BAC twice daily for 2 weeks (Group BAC-W2), 3 weeks (Group BAC-W3), 4 weeks (Group BAC-W4), or 5 weeks (Group BAC-W5). Fluorescein staining, Schirmer's tests, and conjunctival impression cytology were performed before BAC treatment (normal) and on days 0, 7, 14 and 21 after BAC removal. The eyeballs were collected at these time points for immunofluorescence staining, hematoxylin and eosin (HE) staining, and electron microscopy. After removing BAC, the signs of dry eye in Group BAC-W2 lasted one week. Compared with normal, there were still significant differences in the results of Schirmer's tests and fluorescein staining in Groups BAC-W3 and BAC-W4 on day 7 (P,0.05) and in Group BAC-W5 on day 14 (P,0.05). Decreases in goblet cell density remained stable in the three experimental groups at all time points (P,0.001). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21. Conclusions:A stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye).
A good performance of motion capture, which belongs to body sensor network, depends on a reasonable design of MAC protocol. The purpose of this study is to design a reliable and highly extensible protocol for applying in motion capture. The proposed MAC protocol can easily be actualized by the timer in the chip. With this MAC protocol, the network would be built quickly. One or more nodes could be added easily in the net or deleted randomly from the net. In order to verify the superiority of this protocol, a series of experiments were designed. The results showed that the mean of simulation receive frames for node1-node7 from each stage were very close to the original frames. In addition, the final Pocket Loss Rates for node1-node7 were 0.081%, 0.175%, 0.143%, 0.249%, 0.248%, 0.044% and 1.897%, which could be in the error-allowed range. Thus, this protocol is stable and reliable, which can be widely used to capture human movement signal.
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