Valerie Yu1, Dhruva Bhattacharya2, Andrew Webster3, Aditi Bauskar4, Charles Flowers5, Martin Heur5, Shravan K Chintala3, Tatsuo Itakura3, Mark R Wilson6, Joseph T Barr7, Shinwu Jeong8, Mingwu Wang2, M Elizabeth Fini9. 1. MD Program, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. 2. Department of Ophthalmology & Vision Science, University of Arizona College of Medicine, Tucson, AZ, USA. 3. USC Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. 4. PhD Program in Medical Biology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. 5. USC Roski Eye Institute and Department of Ophthalmology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. 6. Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, New South Wales, Australia. 7. The Ohio State University College of Optometry, Columbus, OH, USA. 8. USC Institute for Genetic Medicine, USC Roski Eye Institute and Department of Ophthalmology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. 9. USC Institute for Genetic Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA. Electronic address: mefini@tuftsmedicalcenter.org.
Abstract
PURPOSE: To investigate the relationship between tear concentration of the homeostatic protein clusterin (CLU) and dry eye signs and symptoms, and to characterize tear CLU protein. METHODS: Two independent studies were conducted, one in Tucson (44 subjects), the other in Los Angeles (52 subjects). A cohort study design was employed to enroll patients without regard to dry eye diagnosis. Dry eye signs and symptoms were assessed using clinical tests. Tear samples were collected by Schirmer strip, and also by micropipette at slit lamp when possible. CLU from both sample types was quantified by immunoassay. The relationship between CLU concentration and clinical test scores was determined by Pearson's correlation coefficient (for individual eyes) and multiple linear regression analysis (including both eyes). CLU was also evaluated biochemically by western blotting. RESULTS: In the Tucson cohort, a positive correlation was observed between tear CLU concentration and results of the Schirmer strip test, a measure of tear flow (p = 0.021 includes both eyes). This result was corroborated in the Los Angeles cohort (p = 0.013). The mean tear CLU concentration was 31 ± 14 μg/mL (n = 18 subjects, 33 eyes; range = 7-48 μg/mL). CLU from clinical tear samples appeared biochemically similar to CLU from a non-clinical tear sample and from blood plasma. CONCLUSIONS: Results support the hypothesis that an optimal concentration of tear CLU is important for ocular surface health, and that this drops below the effective threshold in dry eye. Tear CLU measurement might identify patients that could benefit from supplementation. Information about concentration will aid development of therapeutic dosage parameters.
PURPOSE: To investigate the relationship between tear concentration of the homeostatic protein clusterin (CLU) and dry eye signs and symptoms, and to characterize tear CLU protein. METHODS: Two independent studies were conducted, one in Tucson (44 subjects), the other in Los Angeles (52 subjects). A cohort study design was employed to enroll patients without regard to dry eye diagnosis. Dry eye signs and symptoms were assessed using clinical tests. Tear samples were collected by Schirmer strip, and also by micropipette at slit lamp when possible. CLU from both sample types was quantified by immunoassay. The relationship between CLU concentration and clinical test scores was determined by Pearson's correlation coefficient (for individual eyes) and multiple linear regression analysis (including both eyes). CLU was also evaluated biochemically by western blotting. RESULTS: In the Tucson cohort, a positive correlation was observed between tear CLU concentration and results of the Schirmer strip test, a measure of tear flow (p = 0.021 includes both eyes). This result was corroborated in the Los Angeles cohort (p = 0.013). The mean tear CLU concentration was 31 ± 14 μg/mL (n = 18 subjects, 33 eyes; range = 7-48 μg/mL). CLU from clinical tear samples appeared biochemically similar to CLU from a non-clinical tear sample and from blood plasma. CONCLUSIONS: Results support the hypothesis that an optimal concentration of tear CLU is important for ocular surface health, and that this drops below the effective threshold in dry eye. Tear CLU measurement might identify patients that could benefit from supplementation. Information about concentration will aid development of therapeutic dosage parameters.
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