metallothionein and Retinitis-Pigmentosa

Methallothionein (MT) is a low molecular weight cysteine rich metalloprotein. In mammals, there are four isoforms (MT-1, -2, -3, and -4) and they have multiple roles, such as the detoxification of heavy metals, regulating essential metal homeostasis, and protecting against oxidative stress. Recently, accumulating studies have suggested that MTs (especially MT-1, -2, and -3) are an important neuroprotective substance for cerebral ischemia and retinal diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), that are characterized by a progressive retinal degeneration. Oxidative stress and/or zinc toxicity has been implicated as part of the common pathway in these diseases. Studying the expression patterns and functions of MTs may broaden our understanding of the endogenous molecular responses that these diseases trigger, and may help us to develop new therapeutic strategies to treat them. However, the precise roles of MTs within the brain and retina are not fully understood in terms of neuropathological conditions. In this review, we discuss the recent findings focusing on MTs' functions following cerebral ischemia, AMD, and RP.

Topics: Animals; Brain; Brain Ischemia; Humans; Macular Degeneration; Metallothionein; Retina; Retinitis Pigmentosa

To examine in rodent models of retinitis pigmentosa (RP) the expression of the neuroprotectants metallothionein-I and -II and of megalin, an endocytic receptor that mediates their transport into neurons.. Gene and protein expression were analyzed in retinas of rd1 and rds mice and in those of RCS (Royal College of Surgeons) rats of various ages. Glial cell markers (cellular retinaldehyde binding protein, CRALBP; glial fibrillary acidic protein, GFAP; CD11b; and isolectin B4) were used to establish the identity of the cells.. Metallothionein-I and -II gene expression increased with age in normal and degenerating retinas and was significantly greater in the latter. Protein expression, corresponding to metallothionein-I+II, was first observed in rd1 mice in Müller cells at postnatal day (P)12 and in rds mice at P16, coinciding with the onset of GFAP expression in these cells. In RCS rats, the same distribution was observed, but not until P32, long after the onset of GFAP expression. Metallothionein-I+II was observed also in a small number of microglial cells. Megalin was expressed in the nerve fiber layer and in the region of the inner and outer segments in normal animals, but expression in the outer retina was lost with age in degenerating retinas.. Induction of metallothionein-I and -II occurs in the RP models studied and correlates with glial activation. The progressive loss of megalin suggests that transport of metallothionein-I+II into the degenerating photoreceptors (from e.g., Müller cells), could be impaired, potentially limiting the actions of these metallothioneins.

Topics: Animals; Astrocytes; Avidin; Biomarkers; Cyclic Nucleotide Phosphodiesterases, Type 6; Disease Models, Animal; Glial Fibrillary Acidic Protein; In Situ Nick-End Labeling; Low Density Lipoprotein Receptor-Related Protein-2; Metallothionein; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Microglia; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Photoreceptor Cells, Vertebrate; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells; Retinitis Pigmentosa