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M.S. Gregory, A.M. Hohlbaum, A. Marshak–Rothstein, B.R. Ksander; The eye possesses a unique immune privileged environment that contains high levels of modified soluble Fas ligand . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4520.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Fas ligand (FasL) can be expressed in either a membrane–bound or soluble form. Our studies using ocular tumors demonstrated that the different forms of FasL exhibit opposite effects on immune privilege; membrane–bound FasL terminates and soluble FasL enhances immune privilege. The current studies examined the form of FasL constitutively expressed by ocular tissues in: normal, chronically inflamed, and FasL KO eyes. We hypothesize that within the eye there is a high ratio of soluble to membrane Fas ligand that is critical in maintaining immune privilege.Methods and Results: Protein lysates were prepared from whole eyes of DBA/2 mice and analyzed by Western blot using a FasL specific antibody. The ratio of soluble (27kD) to membrane (38kD) FasL was 10:1 in normal eyes, as determined by densitometry using NIH Image. Interestingly, the Western blots also revealed three additional bands (28–31kD) suggesting either glycosylated or isoforms of sFasL were present, making the ratio of total soluble to membrane FasL 45:1. The sFasL and modified forms were all absent from lysates prepared from whole eyes of FasL KO mice. The FasL KO mice were created using the Cre/lox system to delete a small portion of exon 2 from the FasL gene, resulting in a frame shift and a stop codon that prevented FasL transcription. In normal eyes, sFasL was not found in: the central cornea, iris, ciliary body, or posterior segment of the eye. Faint sFasL bands were observed in fresh aqueous humor; the majority of sFasL was located in the trabecular meshwork and/or limbal area. In addition, the modified forms of sFasL were unique to the eye and not found in other immune privileged sites such as the testis. Interestingly, the 27kD and 31kD sFasL bands were completely absent in eyes that lacked immune privilege and displayed chronic inflammation secondary to pigment dispersion syndrome. Conclusions: The eye constitutively expresses modified forms of sFasL that are not found in other immune privileged sites and are lost during chronic ocular inflammation. These data imply that the eye expresses unique forms of sFasL that may be critical in maintaining ocular immune privilege.
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