Immunocytochemical localization of thrombomodulin in the aqueous humor passage of the rat eye

Daimon, Tateo; Kazama, Mutsuyoshi; Miyajima, Yukari; Nakano, Masahiko

doi:10.1007/s004180050153

Cited by 19 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rodents share similar anatomical and developmental characteristics in the anterior segment, especially in the aqueous outflow pathway, with those of the human [23]. Advances in IOP measurements in small eyes have also accelerated the use of rodents in glaucoma research [24,25].…”

Section: Discussionmentioning

confidence: 99%

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Fonseca

Martínez-Águila

Lara

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

Glaucoma is a neurodegenerative disease that produces blindness. The main factor associated with this disease is an abnormally elevated intraocular pressure (IOP). To date, some attempts have been made to demonstrate the role of nucleotides modulating IOP, but never in a model of glaucoma. The DBA/2J mouse is an animal that develops the pathology spontaneously, starting from the typical rise in IOP at 9 months of age. Using this animal model, together with a control mouse, C57BL/6J, it has been possible to monitor the elevation in IOP in the glaucomatous mice and to check the ability of the dinucleotide diadenosine tetraphosphate AKA Ap 4 A to reduce IOP. The topical application of Ap 4 A when IOP is maximal (9-12 months) reduced IOP 30.6 ± 6.6% in the DBA/2J and 17.9 ± 4.0% in the C57BL/ 6J mice. Concentration response curves in both animal strains produced similar pD2 values; these being 4.9 ± 0.5 and 5.1 ± 0.4 for the normotensive C57BL/6J and the glaucomatous DBA/2J respectively. Antagonist studies showed differences between the control and the glaucomatous animals. In particular, the main receptor reducing IOP in the control animal was the P2Y 1 receptor and in the glaucomatous model the P2Y 6 , although the participation of other P2 receptors cannot be ruled out. The long-term effect of Ap 4 A applied three times a week for 3 months showed a clear stop in the elevation of IOP in the glaucomatous model, thus indicating the possibility of using Ap 4 A as an effective compound for the treatment of glaucoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Fonseca

Martínez-Águila

Lara

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…Rabbit antiserum against rat lung TM was obtained as described previously (Daimon et al 1997). An IgG fraction of the antiserum was used in the immunostaining.…”

Section: Antibodymentioning

confidence: 99%

“…An IgG fraction of the antiserum was used in the immunostaining. It was isolated from rabbit serum using Affigel protein A (BioRad Laboratories, CA, USA) and was monospecific as determined by western blots (Daimon et al 1997).…”

Section: Antibodymentioning

confidence: 99%

“…TM binds thrombin and changes the substrate specificity of thrombin toward protein C. The thrombin-TM complex activates protein C. Activated protein C in turn inactivates clotting factors Va and VIIa and plasminogen activator inhibitor type I, thus shifting the hemostatic balance to anticoagulation (Lentz and Sadler 1994). However, TM has not only been found in the vascular endothelial cells but also in some types of non-vascular cells, including the mesothelia of the pleura, pericardium, and synovial membrane (Boffa et al 1987), brain astrocytes (Pindon et al 1997), ciliary epithelia (Daimon et al 1997), and keratinocytes (Daimon and Nakano 1999). The function of TM outside vessels is not known, although this protein was postulated to play roles during embryogenesis in addition to anticoagulation (Imada et al 1990;Healy et al 1995).…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Localization of thrombomodulin in pericryptal fibroblasts of the rat duodenum

Daimon

Okuma

2004

Histochemistry and Cell Biology

View full text Add to dashboard Cite

Thrombomodulin (TM) contributes to the inactivation of thrombin which activates protein C, a major anticoagulant and anti-inflammatory protein. This report describes the distribution and localization of TM in the rat duodenum by light and electron microscopic immunohistochemistry. In addition to the endothelium of the entire vasculature, TM was found on the non-vascular structures, cellular networks of pericryptal fibroblasts surrounding the bases of the glandular crypts. TM was localized on the plasma membrane of the pericryptal fibroblasts which existed in the pericryptal spaces between the basal lamina of the epithelium and the collagenous sheets around the base of the crypt. TM-immunoreactive pericryptal fibroblasts were stellate-shaped cells and contacted with each other by their cytoplasmic processes forming an anastomosing syncytium around the base of the crypt. In contrast to pericryptal fibroblasts, TM was not localized in subepithelial fibroblasts in the villi or smooth muscle cells in the lamina muscularis mucosae and the muscularis. The functional significance of TM in pericryptal fibroblasts is discussed.

show abstract

“…Rats were selected for this study because they share similar anatomic and developmental characteristics in the anterior segment with those of the human. [26][27][28][29] Therefore, aqueous-humor-dynamic studies in rats may be more predictive of the response in humans than those from other nonprimate laboratory animals. Results from these studies support the idea that both TNF-␣ and MMPs play a role in prostaglandin-induced changes in IOP.…”

mentioning

confidence: 99%

Latanoprost-Induced Changes in Rat Intraocular Pressure: Direct or Indirect?

Husain

Yates

Crosson

2008

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Introduction: The topical application of prostaglandin F 2␣ (FP)-receptor agonists has been shown to significantly lower intraocular pressure (IOP) in humans and is now considered the first-line treatment for ocular hypertension. Despite the prominent role FP-receptor agonists play in the treatment of glaucoma, our understanding of how these agents lower IOP remains incomplete. The present study was designed to evaluate the role of matrix metalloproteinase (MMP) activation and the cytokine, tumor necrosis factor alpha (TNF-␣), in latanoprost-induced changes in IOP. Methods: Changes in IOP following an acute topical administration of latanoprost (60 ng) in normotensive Brown Norway rats were evaluated by means of a commercially available rebound tonometer. To examine the role of MMPs and TNF-␣ in this response, the rats were pretreated with a broad-spectrum MMP inhibitor, GM-6001 (100 g), or the TNF-␣ inhibitor, thalidomide (25 g). Results: The topical administration of latanoprost (60 ng) alone produced a biphasic change in ipsilateral IOP: an initial hypertension (4.21 Ϯ 0.52), followed by a prolonged hypotension (Ϫ4.79 Ϯ 0.65). In rats, pretreatment with GM-6001 blocked the latanoprost-induced reduction in IOP but did not prevent the initial rise in IOP. Pretreatment with thalidomide also blocked the ocular hypotension induced by latanoprost; however, thalidomide pretreatment enhanced the duration of the initial hypertension. Conclusions: These results provide evidence that the secretion and activation of MMPs and the release of TNF-␣ play a central role in the ocular hypotension induced by FP-agonists. The administration of FP-agonists appears to lower IOP directly by inducing the activation of MMPs within the ciliary body, leading to improved uveoscleral outflow and indirectly through the release of TNF-␣ within the ciliary body. Secreted TNF-␣ may then activate TNF-receptors in the uvea and trabecular meshwork, increasing both uveoscleral and conventional outflow.

show abstract

Immunocytochemical localization of thrombomodulin in the aqueous humor passage of the rat eye

Cited by 19 publications

References 14 publications

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

Localization of thrombomodulin in pericryptal fibroblasts of the rat duodenum

Latanoprost-Induced Changes in Rat Intraocular Pressure: Direct or Indirect?

Contact Info

Product

Resources

About