Abstract
Purpose: :
Angiopoietin-like 7 (ANGPTL7), also known as cornea-derived transcript 6 (CDT6) is a member of the angiopoietin-like family of proteins. We have previously shown that cultured human trabecular meshwork (TM) cells transfected with ANGTPL7 express more collagen type I. The potential to alter collagen homeostasis makes ANGPTL7 a candidate for involvement in glaucoma pathogenesis. To test this hypothesis, we investigated the expression level of ANGTPL7 in a human glaucoma patient and in a mini-pig model of experimentally induced glaucoma.
Methods: :
The expression pattern of ANGPTL7 in whole eyes of normal human, dog, pig and monkey was determined by immunohistochemistry (IHC). Expression of ANGPTL7 in the TM and lamina cribrosa (LC) were compared by IHC between a pair of human cadaver eyes from a patient with glaucoma in only one eye. Elevated intraocular pressure (IOP) was induced in 3 mini-pigs in one eye by cauterizing episclera veins, as previously reported, and ANGTPL7 protein concentration in aqueous humor (AH) was analyzed by Western blot.
Results: :
Similar expression patterns of ANGPTL7 were found in all species tested, with the highest level found in the sclera. ANGTPL7 expression was low in normal human and monkey TM. In the LC of all 4 species, patches of ANGPTL7 immunoreactivity were associated with the cribriform plates. Significant glaucomatous cupping was observed in one eye, but not in the fellow eye of the human donor, consistent with the documented clinical history. The expression levels of ANGPTL7 in both TM and LC of the glaucomatous eye were significantly higher in comparison to the fellow eye. Moderate elevation of IOP (average of 4 mmHg) was induced in one eye in all three mini-pigs. ANGPTL7 protein concentration was elevated in glaucomatous eye in comparison to the normal fellow eye in all 3 mini-pigs.
Conclusions: :
The similar pattern of expression across all species tested suggests a possible conserved function of ANGPTL7. The increased concentration of ANGPTL7 in glaucomatous AH of mini-pigs is consistent with our previous findings with human and dog AH. Together our work is consistent with the hypothesis that ANGPTL7 may be elevated in glaucomatous AH where it could affect collagen production, and possibly contribute to increased outflow resistance. It may also contribute to optic nerve axonal damage in glaucoma by inducing extracellular matrix deposition in the LC.
Keywords: aqueous • extracellular matrix • lamina cribrosa