Abstract:

Purpose To determine whether the incidence of and susceptibility to climatic droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal disease, is influenced by the genetic background of the individuals who exhibit the disorder. Methods To determine whether the disease expression was influenced by the genetic ancestry of CDK cases in native Mapuche of the northwest area of Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient) population, while 24 were part of the control group. The analysis revealed the maternal and paternal lineages that were present in the two study groups. Results This analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. There was no significant difference in the frequencies of mtDNA haplogroups between the CDK patient and control groups. Although the Y-chromosome data revealed differences in specific haplogroup frequencies between these two groups, there was no statistically significant relationship between individual paternal genetic backgrounds and the incidence or stage of disease. Conclusions These results indicate a lack of correlation between genetic ancestry as represented by haploid genetic systems and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears to play less of a role in CDK expression than for other complex diseases linked to bioenergetic processes. However, further analysis of the mtDNA genome sequence and other genes involved in corneal function may reveal the more precise role that mitochondria play in the expression of CDK.

Author affiliation: Schurr, Theodore G.. University Of Pennsylvania. Penn Museum Of Archaeology And Anthropology; United State of America;

Author affiliation: Dulik, Matthew C.. University Of Pennsylvania. Penn Museum Of Archaeology And Anthropology; United State of America;

Author affiliation: Cafaro, Thamara Analia. Consejo Nacional de Investigaciones Científicas y Técnicas.Centro Científico Tecnológico - CONICET - Cordoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina;

Author affiliation: Suarez, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas.Centro Científico Tecnológico - CONICET - Cordoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina;

Author affiliation: Urrets-Zavalia, Julio A.. Universidad Catolica de Cordoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola. Dto de Oftalmologia;

Author affiliation: Serra, Horacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas.Centro Científico Tecnológico - CONICET - Cordoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina;

Abstract:

PURPOSE. Climatic droplet keratopathy (CDK) is a degenerative disease of the cornea with possible involvement from matrix metalloproteinases (MMPs). Therefore, the authors investigated histologic distribution, levels, and molecular forms of MMP- 2 and MMP-9, as well as tear fluid levels of MMPs and cytokines in CDK patients. They additionally examined UV-B-irradiation effect on production of gelatinases and cytokines by human corneal epithelial (HCE) cell culture model. METHODS. Tears were collected from 20 unrelated individuals (10 with CDK and 10 controls). CDK affected corneas were haematoxylin-eosin stained and the presence and distribution of MMP-2 and MMP-9 was examined using immunohistochemistry. Gelatinases and cytokine secretion was measured in tears and supernatants from UV-B-exposed HCEs by immunoblotting, gelatin zymography, and protein array, respectively. RESULTS. MMP-2 and MMP-9 values were significantly higher in tears collected from CDK patients than healthy controls and were accompanied by pro-inflammatory cytokine secretion. Immunohistochemistry showed that MMP-2 was expressed at the basement membrane zone in both control and affected corneas, but also marked the edges of the granular CDK deposits; MMP-9 expression was restrained to basal layers of the epithelium and was markedly induced in CDK corneas. In HCE cells, UV-B increased gelatinase secretion, with a striking effect on MMP-9, and was preceded by pro-inflammatory cytokine release. CONCLUSIONS. The authors demonstrate that the corneal epithelium could participate in CDK development as a source of cytokines and gelatinases. Additionally, in HCE cells, UV-B- modulated cytokine and subsequent MMP secretion. Local inhibition of cytokine secretion and gelatinases may prevent CDK progression. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Author affiliation: Holopainen, Juha M.. University Of Helsinski; Finlandia

Author affiliation: Robciuc, Alexandra. University Of Helsinski; Finlandia

Author affiliation: Cafaro, Thamara Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

Author affiliation: Suarez, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

Author affiliation: Konttinen, Yrjö T.. University Of Helsinski; Finlandia

Author affiliation: Alkatan, Hind M.. The Eye Center and The Eye Foundation for Research in Ophthalmology; Arabia Saudita

Author affiliation: Tabbara, Khalid F.. The Eye Center and The Eye Foundation for Research in Ophthalmology; Arabia Saudita

Author affiliation: Tervahartiala, Taina. University Of Helsinski; Finlandia

Author affiliation: Sorsa, Timo. University Of Helsinski; Finlandia

Author affiliation: Urrets Zavalía, Julio Alberto. Universidad Catolica de Córdoba. Facultad de Medicina. Clinica Universitaria Reina Fabiola. Dto de Oftalmologia; Argentina

Author affiliation: Serra, Horacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina