These microarray results provide clues to understanding the molecular pathways underlying photoreceptor degeneration and indicate directions for future studies. In addition, comparisons of normal and degenerated retina identified numerous genes and ESTs that are potentially enriched in rod photoreceptors.
Increased mRNA and protein levels of the iron-regulating proteins transferrin, ceruloplasmin, and ferritin are present in glaucoma. Together, these results suggest the involvement of iron and copper metabolism and associated antioxidant systems in the pathogenesis of glaucoma.
These data demonstrate that transferrin expression is increased in the retinas of patients with AMD relative to those of healthy control patients of comparable age. Along with previous studies that have demonstrated elevated iron levels in AMD retinas, early onset drusen formation in a patient with retinal iron overload resulting from aceruloplasminemia, and retinal degeneration with some features of macular degeneration in the iron-overloaded retinas of ceruloplasmin/hephestin knockout mice, the present study suggests that altered iron homeostasis is associated with AMD.
1. A widespread mechanism of slow excitation throughout the nervous system involves overlapping changes in nonselective ion conductance and K+ conductance. We used whole cell patch-clamp recording to characterize such a nonselective conductance induced by neurotensin (NT) and other neurotransmitters in immunocytochemically identified dopaminergic neurons cultured from the rat ventral tegmental area (VTA). 2. The NT-induced inward current consisted of an initial peak and later "hump." The response was blocked reversibly by the nonpeptide NT-receptor antagonist SR48692, suggesting that it resulted from activation of NT receptors. 3. The channel was almost equally permeable to Na+ and K+, as determined from the reversal potential shift upon switching from Na+- to K(+)-containing external solution. The permeability of Cs+ was similar to that of Na+, as determined from the zero-current equation and average reversal potential in the 75 mM Na+ solution. Cl- was not significantly permeable. 4. In Ca(2+)-free external solution, the NT-induced current showed a fourfold increase in amplitude, and in high Mg2+ (20 mM) external solution, the NT-induced current showed an 80% decrease in amplitude, suggesting that external Ca2+ and Mg2+ could block the nonselective conductance. 5. The NT response was unaffected by loading the neurons with either the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or with 1 mM ca2+. The nonselective conductance was therefore not Ca2+ activated. 6. Loading the neurons with cyclic GMP or cyclic AMP (each with the phosphodiesterase inhibitor isobutyl-methylxanthine) did not affect the NT response. The NT-induced nonselective conductance was therefore not cyclic nucleotide-activated. 7. The latency of the NT response was long (> or = 185 ms, average 406 ms, 30 degrees C), indicating that NT did not induce the conductance through ligand-gated channels. Thus, NT activated a slow nonselective cation conductance. 8. Neurokinin B, a metabotropic glutamate agonist, and muscarine elicited responses similar to the NT response. The NT response could be elicited after desensitizing the responses to these other neurotransmitters, indicating receptor specificity in the activation of the nonselective conductance.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.