Stromal-Epithelial Interactions in the Cornea

Wilson, Steven E.

doi:10.1007/978-1-4615-5389-2_35

Cited by 49 publications

(70 citation statements)

References 31 publications

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“…Studies of KC have demonstrated the presence of alterations in the corneal epithelium 36 and stroma. 37 But complementary and useful information can also be obtained by biochemical analysis of tears, which are relatively easy to obtain. The stable tear film is prerequisite for the proper functioning of optical and metabolic eye.…”

Section: Discussionmentioning

confidence: 99%

Changes in tear protein profile in keratoconus disease

Acera

Vecino

Rodríguez-Agirretxe³

et al. 2011

Eye

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Purpose To analyze tear protein profile variations in patients with keratoconus (KC) and to compare them with those of control subjects. Subjects and methods Tears from 12 normal subjects and 12 patients with KC were analyzed by two-dimensional gel electrophoresis (2-DE) and liquid chromatography-mass spectrometry (LC-MS). Analysis of the 2-DE gels was performed using Progenesis SameSpots software (Nonlinear Dynamics). Proteins exhibiting high variation in expression levels (P-value o0.05) were identified using matrix-assisted laser desorption/ionization-TOF spectrometry. For LC-MS analysis, a label-free quantification approach was used. Tears were digested with trypsin, subjected to data-independent acquisition (MS E ) analysis, and identified proteins were relatively quantified using ProteinLynx Global Server software (Waters). Results The 2-DE and LC-MS analyses revealed a significant decrease in the levels of members of the cystatin family and an increase in lipocalin-1 in KC patients. A 1.43-fold decrease was observed for cystatin-S by 2-DE, and 1.69-and 1.56-fold for cystatin-SN and cystatin-SA by LC-MS, respectively. The increase in lipocalin-1 was observed by both methods with fold changes of 1.26 in the 2-DE approach and 1.31 according to LC-MS. Significant protein upregulation was also observed for Ig-j chain C and Ig J chain proteins by 2-DE. Levels of lipophilin-C, lipophilin-A, and phospholipase A2 were decreased in tears from KC patients according to LC-MS. Serum albumin was found to be increased in KC patients according to LC-MS. Conclusion The results show differences in the tear protein profile of KC and control subjects. These changes are indicative of alterations in tear film stability and in interactions with the corneal surface in KC patients.

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Section: Discussionmentioning

confidence: 99%

Changes in tear protein profile in keratoconus disease

Acera

Vecino

Rodríguez-Agirretxe³

et al. 2011

Eye

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“…Interleukin-1α and β modulate several important components of the stromal response to injury, including Fas/Fas ligand-mediated regulation of keratocyte apoptosis (Wilson et al, 1996;Mohan et al, 1997), keratocyte production of paracrine mediators hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) that regulate epithelial proliferation, migration and differentiation (Weng et al, 1997;Wilson et al, 1999), keratocyte production of collagenases and metalloproteinases (Girard et al, 1991;Li et al, 2003;Xue et al, 2003), and keratocyte production of chemokines . Biswas et al (2004) also demonstrated that IL-1 receptor antagonist reduced the influx of cells of the innate and adaptive immune response into the cornea in a mouse herpes simplex model.…”

Section: Discussionmentioning

confidence: 99%

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

Stapleton

Chaurasia

Medeiros

et al. 2008

Experimental Eye Research

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Interleukin (IL)-1α and β are important modulators of many functions of corneal epithelial and stromal cells that occur following injury to the cornea, including the influx of bone marrow-derived inflammatory cells into the stroma attracted by chemokines released from the stroma and epithelium. In this study, we examined the effect of topical soluble IL-1 receptor antagonist on bone marrowderived cell influx following corneal epithelial scrape injury in a mouse model. C57BL/6 mice underwent corneal epithelial scrape followed by application of IL-1 receptor antagonist (Amgen, Thousand Oaks, CA) at a concentration of 20 mg/ml or vehicle for 24 h prior to immunocytochemical detection of marker CD11b-positive cells into the stroma. In two experiments, topical IL-1 receptor antagonist had a marked effect in blocking cell influx. For example, in experiment 1, topical IL-1 receptor antagonist markedly reduced detectible CD11b-positive cells into the corneal stroma at 24 h after epithelial injury compared with the vehicle control (3.5 ± 0.5 (standard error of the mean) cells/400× field and 13.9 ± 1.2 cells/400× field, respectively, p < 0.01). A second experiment with a different observer performing cell counting had the same result. Thus, the data demonstrate conclusively that topical IL-1 receptor antagonist markedly down-regulates CD-11b-positive monocytic cell appearance in the corneal stroma. Topical IL-1 receptor antagonist could be an effective adjuvant for clinical treatment of corneal conditions in which unwanted inflammation has a role in the pathophysiology of the disorder.

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“…It is possible that in keratoconus as well as in the Itgb1 −/− corneas there is increased stress on the keratocytes due to loss of integrity of the matrix, affecting the normal physiology of keratocytes. We can only speculate presently that such stress could disrupt the growth factormediated communications between the keratocyte and corneal epithelium (Wilson et al 1999;Imanishi et al 2000) and is a cause for the reduced cell division of basal epithelia in the Itgb1 −/− corneas (Parapuram et al 2011). The necessity of a mature matrix is again evident as the swelling pressure caused by hydrophilic glycosaminoglycans is counteracted by the lamellar tension and the cohesive forces between lamellae (Klyce et al 1971;Smolek and McCarey 1990;Dupps and Wilson 2006).…”

Section: Stromal Ecm Maturationmentioning

confidence: 99%

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

Parapuram

Hodge

2014

J. Cell Commun. Signal.

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Several studies have established the role of activated corneal keratocytes in the fibrosis of the cornea. However, the role of keratocytes in maintaining the structural integrity of a normal cornea is less appreciated. We focus on the probable functions of integrins in the eye and of the importance of integrin-mediated keratocyte interactions with stromal matrix in the maintenance of corneal integrity. We point out that further understanding of how keratocytes interact with their matrix could establish a novel direction in preventing corneal pathology including loss of structural integrity as in keratoconus or as in fibrosis of the corneal stroma.Keywords Cornea . Keratocytes . Corneal stroma . Extracellular matrix . Integrins . KeratoconusThe simple cellular organization of the cornea is belied by its fascinating specialization for transparency. The cornea has three main tissue layers, the outer epithelium, the stroma in the middle and the inner endothelial layer. The stromal connective tissue, the layer mainly responsible for the corneal configuration, constituting nearly 80 % of the thickness of the cornea, is extremely resilient, capable of resisting intraocular pressure and protecting the posterior structures of the eye. The stromal tissue consists of lamellae of orthogonally arranged collagen fibrils surrounded by proteoglycans; in between the lamellae of collagen are found the keratocytes. The nearorderly arrangement of collagen lamellae, the narrow diameter of the collagen fibrils, regular interfibrillar space, associated proteoglycans and the expression of crystalline proteins in the keratocytes (Birk 2001;Kao and Liu 2002;Jester et al. 2007; Hassell and Birk 2010) are some of the main factors responsible for corneal transparency. Consequently, the factors affecting corneal transparency such as fibrotic changes due to disease or injury are problems primarily associated with the stroma. Thus it is important to achieve further understanding of the mechanisms by which the stroma acquires and maintains its structural integrity and its transparency.

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Stromal-Epithelial Interactions in the Cornea

Cited by 49 publications

References 31 publications

Changes in tear protein profile in keratoconus disease

Changes in tear protein profile in keratoconus disease

Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration into the cornea

The integrin needle in the stromal haystack: emerging role in corneal physiology and pathology

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