Abstract
Purpose: :
Glaucoma is an optic neuropathy that affects over 60 million people worldwide. Gene expression studies in models of glaucoma suggest that ceruloplasmin (Cp), a multi–nuclear "blue" copper oxidase, may be involved in the pathogenesis of this disease. Cp serves as an antioxidant by scavenging free radicals and oxidizing ferrous iron. The retina is very dependent on iron, however this need for iron also makes it especially vulnerable to damaging free radicals. Iron accumulation occurs in many neurodegenerative diseases within the CNS, but retinal iron levels in glaucoma have not been extensively studied. The purpose of this study was to examine retinal expression of Cp and other iron handling genes in the DBA/2 mouse model of glaucoma.
Methods: :
Using RT–PCR the expression of Cp and various iron handling genes was examined in DBA/2 mice with low and high intraocular pressure (IOP). Immunocytochemistry was used to localize Cp protein within low and high IOP DBA/2 retinas. Finally, retinal iron deposition in low and high IOP DBA/2 mice was examined histochemically.
Results: :
Message for both the secreted and the GPI–linked form of Cp were detected in retinas from low and high IOP DBA/2 mice, as was transferrin and transferrin receptor 2. In addition, lipocalin–2, megalin, ferroportin and lactoferrin mRNA expression was observed in high IOP retinas. Cp protein was observed throughout the DBA/2 retina with more intense staining localized to the plexiform layers and the ganglion cell layer. In high IOP retinas, Cp expression appeared to be increased within these layers when compared to low IOP retinas. Slight differences in retinal iron deposition were observed between low and high IOP DBA/2 retinas.
Conclusions: :
Cp and other iron handling genes are expressed in the retinas of low and high IOP DBA/2 mice. Although Cp protein expression was increased in high IOP retinas, it does not appear this up–regulation is due to increased iron deposition. Further investigation of Cp is necessary in order to determine the role of Cp within the retina during glaucoma progression.
Keywords: retinal glia • antioxidants • neuroprotection