Sunday 1 November

Purpose: The serine protease inhibitor, neuroserpin, is predominantly expressed in neural tissues and is well expressed in the vitreous and retina. There is evidence of involvement of proteases in matrix remodelling and mediating damage to the optic nerve head and RGCs in glaucoma. As neuroserpin is linked to selectively inhibiting proteases, mainly plasminogen activators and plasmin, we evaluated changes in its expression and inhibitory activity. Methods: Human retinal and vitreous tissues from donated eyes were examined from control (age: control 64.8 ± 10.16, n = 12) and glaucoma subjects (age: 71.6 ± 8.67, n = 12). Retinal samples from rats exposed to experimentally elevated intraocular pressure (IOP) by microbead injections were also examined and compared with the control eyes. Immunoprecipitation followed by immunoblotting were carried out to assess changes in the neuroserpin expression. Neuroserpin activity was also assessed by immuno-precipitation followed by in-gel-zymography. Results: The plasmin inhibitory activity of neuroserpin was significantly reduced in the vitreous samples in the human glaucoma group compared to controls as revealed by immunoprecipitation followed by in-gel-zymography (n = 12, P < 0.0025). No significant changes were however observed in the neuroserpin expression in the human vitreous samples. Significantly decreased neuroserpin activity was also observed in the rat retinas exposed to experimentally increased IOP (P < 0.03, n = 5) as well as in retinal tissues from human optic nerve head region (P < 0.04; n = 6). Conclusions: Impaired neuroserpin activity is observed in human glaucoma tissues as well as in rodent model of experimentally elevated IOP, indicating a potential reduction of proteolytic inhibition in glaucoma. This could facilitate increased structural damage to tissues.1 page(s