Monday, July 25, 2011

Abstract: Role of EMMPRIN in dry eye

Extracellular Matrix Metalloproteinase Inducer Modulates Epithelial Barrier Function through a Matrix Metalloproteinase-9-Mediated Occludin Cleavage: Implications in Dry Eye Disease.

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure.

Am J Pathol. 2011 Jul 18. [Epub ahead of print]
Huet E, Vallée B, Delbé J, Mourah S, Prulière-Escabasse V, Tremouilleres M, Kadomatsu K, Doan S, Baudouin C, Menashi S, Gabison EE.
CRRET Laboratory, Université Paris-Est, CNRS, Créteil, France; Department of Bioengineering, Institute of Technology, Université Paris-Est, Créteil, France.

Abstract: Dry eye and hepatitis C

[Ocular surface and hepatitis C].
[Article in Portuguese]

To evaluate the outcomes of the tests used for dry eye diagnosis in patients with hepatitis C virus, and to verify if there is any relationship between the duration of illness and intensity of ocular surface changes.

25 patients with hepatitis C virus without treatment, and 29 patients with negative serologic tests for hepatitis C virus were selected. Biomicroscopy, tear film crystallization test, tear film break-up time, evaluation of the corneal staining with 1% fluorescein sodium, Schirmer I test, ocular surface staining with 1% rose bengal and esthesiometry were performed in both groups.

In the Schirmer I test, the group of patients with hepatitis C displayed lower values in both eyes (OR p=0.0162; OS p=0.0265). For the tear film break-up time, there was a lower score in the group with hepatitis C, but it was statistically significant only in the left eye (p=0.0007). Regarding the ocular surface damage, the rose bengal staining test showed a higher average in the hepatitis group in both eyes (right p=0.0008; left p=0.0034). There was a difference in the average esthesiometry between the groups, being the average lower in infected patients (OR p=0.0006; OS p=0.0015). There was no linear association between time of hepatitis C infection and intensity observed in dry eye tests.

Hepatitis C virus infection causes dry eye. Further researches are necessary to establish the physiopathology and the relationship with Sjögren syndrome.

Arq Bras Oftalmol. 2011 Apr;74(2):97-101.
Gomes RL, Marques JC, Albers MB, Endo RM, Dantas PE, Felberg S.
Setor de Catarata, Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brasil.

Abstract: Inflammation and dry eye (aqueous vs MGD)

This is a really interesting study looking at cytokines of patients with healthy tears, aqueous deficient dry eye and MGD dry eye. From this perspective, the MGD eye looks more like a healthy eye than an aqueous deficient eye.

Pro-inflammatory cytokine profiling of tears from dry-eye patients by means of antibody-microarrays.

In the pathogenesis of keratoconjunctivitis sicca immune processes are thought to play an important role. However, the exact details of the pathomechanisms are still unknown. In this study we analyzed the expression patterns of pro-inflammatory cytokines in the tears of patients suffering from different subtypes of dry-eye.

143 subjects subdivided into healthy controls (CTRL, n=38), patients having an aqueous deficient dry-eye (DRYaq, n=35), patients showing changes of the lipid-layer (DRYlip, n=36) or a combination of both (DRYaplip, n=34) were examined. Expression patterns of proteins, e.g. IL-1β, IL-6, ITNFα and IFNγ, were examined using an advanced antibody microarray approach.

We detected several highly significant differences in the cytokine levels of dry-eye patients compared to healthy controls. In comparison to healthy subjects, patients suffering from aqueous deficient dry-eye or those with a combined pathogenesis showed elevated levels for most of the tested proteins. E.g. IL-1-β was found to be elevated 2.4 fold in DRYaq patients, respectively 2.75 fold in DRYaqlip patients (both P<8.00E-6). The detected protein amounts of patients suffering from dry-eye induced by lipid layer changes and healthy controls showed only minimal differences (fold increase/decrease for all proteins >1.2, P>0.5).

The similarity between profiles of healthy controls and patients with a lipid layer induced dry-eye justifies the assumption that the pathomechanism of this dry-eye subtype is rather based on other mechanisms than inflammation, whereas it seems to be the case for patients suffering from aqueous deficient dry-eye.

Invest Ophthalmol Vis Sci. 2011 Jul 20. [Epub ahead of print]
Boehm N, Riechardt AI, Wiegand M, Pfeiffer N, Grus FH.
. Experimental Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Germany.