Aging process is accompanied by an increase of tissue transglutaminase in human retinal pigment epithelium

Abstract

Abstract: : Purpose: Cross linking has been suggested as one of the mechanisms involved in the aging process. Among the various cross linking reactions, transglutaminase (TG) catalyzed cross linking activity plays a role in aging. We investigated the age related expression and activity of tissue transglutaminase (tTG) and its reaction product epsilon–gamma–glutamyl lysine (e–g) bonds. Methods: The posterior pole of 18 human donors ranging from 18 to 80 years were incubated with dansyl–cadaverine to demonstrate active TG. Localization of tTG and its reaction product e–g was investigated immunohistochemically. RPE from 12 eyes was analyzed for tTG expression by RT–PCR and Western blot analysis. Results: A faint staining of tTG was observed in RPE of donors until the age of 36. The RPE of old donors (>63years) showed a marked staining. Similar results were found for the extra cellular tTG activity. RT–PCR analysis demonstrated an increase of mRNA expression in the RPE of old eyes about 3 fold. Western blot analysis showed a 4 fold expression of tTG compared to young donors. This increased aktivity was accompanied by an increased expression of e–g bonds in the RPE as well as in Bruch's membrane. Conclusions: An increased expression and activity of tTG was demonstrated during the aging process of the RPE. These findings may play an important role in age related diseases such as macular degeneration.

Keywords: age–related macular degeneration