Anti-CLU monoclonal antibody, clone 3R3/2

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 mu g/mL (n=18 subjects, 33 eyes; range=7-48 mu g/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.

Male infertility is becoming a rapidly growing problem around the world, mainly in the highly developed countries. Seminal proteome composition seems to be one of the crucial factors of the proper course of fertilization - clusterin (CLU) is among the most important ones. CLU, as one of the crucial seminal plasma glycoproteins, plays a very important role in sperm capacitation and immune tolerance in the female reproductive tract. CLU is also known as a sensitive marker of oxidative stress. It has six n-glycosylation sites and also exhibits chaperone activity. An analysis of changes in the profile and degree of CLU glycosylation may shed some new light on the molecular mechanisms of the fertilization process and may be used as an additional diagnostic marker of male fertility. This study constitutes a review of the recently available literature concerning human seminal CLU, including changes in its glycosylation, analyzed in the context of human reproduction.