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Inside IOVS 2001
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July 2001 |
New Insights into the Action(s) of Old Biochemical Friends
TGF-b and the Cornea
Hayashida-Hibino et al. (p. 1691) employed cDNA expression array system to investigate the function of TGF-bs in human cultured corneal epithelial cells. The authors identified that TGF-b1 dramatically regulates gene expression. TGF-b1 affected the expression levels of approximately 300 genes. The vast majority of these genes were downregulated. TGF-b1 may be essential for maintenance of corneal epithelium through the control of signal-transduction pathways. This study will open a novel approach to elucidate the molecular mechanism of regulatory systems mediated by TGF-b1 in epithelia.
Ferritin and the Lens
Oxidative damage is a hallmark of cataractogenesis and virtually all oxidative damage is catalyzed by Fe. Therefore it is fundamentally important to understand Fe metabolism in the lens. The Fe storage protein, ferritin, which is essential to cellular antioxidant defense, contains 24 subunits of two different types, heavy (H) and light (L). The ratio of these subunits influences Fe storage and distribution within the cell. The H:L ratio in cultured lens epithelial cells was altered by overexpression of H or L chain. Goralska et al. (p. 1721) found that cells overexpressing H chain had increased Fe storage and resistance to UV damage.
Ferritin and Schlemm’s Canal
Ethier and Chan (p. 1795) perfused human eyes with either cationic or anionic ferritin at similar concentrations. The surprising finding is that cationic ferritin perfusion reduced facility by 66% compared to anionic ferritin perfusion (P<0.00001), even though transmission electron microscopy showed as much (or more) anionic ferritin in the JCT and intertrabecular spaces. By scanning electron microscopy, cationic ferritin accumulated at intercellular margins of the inner wall of Schlemm’s canal. The authors speculate that cationic ferritin partially or completely blocked intercellular clefts in the inner wall of Schlemm’s canal. These clefts may be “choke points” where a small amount of blockage has a big effect on facility.Aquaporin-1 and the TM
Human trabecular meshwork (TM) cells express aquaporin-1 in vivo, however, its role in aqueous outflow facility is unknown. Two adenovirus constructs containing aquaporin-1 cDNA in the sense or antisense orientation were used to control expression of aquaporin-1 protein in human TM cells in vitro. Using these constructs in three different experimental paradigms, Stamer et al. (p. 1803) demonstrate that aquaporin-1 expression affects resting cell volume and subsequently paracellular permeability of TM cells. Since intracellular volume of TM cells affects the bulk flow of aqueous humor through the conventional outflow pathway, these data indicate that aquaporin-1 expression may influence aqueous outflow facility in vivo.
Arachidonic Acid and the Cornea
In nonexcitable cells, K+ channels are thought to participate in developmental regulation as well as in “housekeeping” functions. The patch-clamp study by Takahira et al. (p. 1847) revealed that arachidonic acid (AA) stimulates a background K+ channel and inhibits a voltage-gated K+ channel in bovine corneal epithelial cells. AA seemed to directly modulate them since some other fatty acids exhibited similar modulation.
Cystatin C and ROS
Cystatin C is a secreted cysteine protease inhibitor present in cerebrospinal fluid, semen and other body fluids. Wassélius et al. (p. 1901) have identified, characterized and localized cystatin C in the retina and found it to be predominantly present in the retinal pigment epithelium. Cystatin C is a strikingly good cathepsin S inhibitor and cathepsin S in turn activates cathepsin D, one of the major proteases involved in outer segment degradation. The observation opens the possibility that cystatin C is important for the regulation of outer segment degradation, and imbalances in the cystatin C/cathepsin S/cathepsin D system are then also conceivable as causes for retinal degenerative diseases.
Neurocan/Phosphacan and the Retina
Neurocan and phosphacan are nervous tissue-specific chondroitin sulfate proteoglycans that are highly expressed in developing rat retina. Inatani et al. (p. 1930) examined neurite outgrowth from cultivated retinal ganglion cells (RGCs) on poly-L-lysine-conditioned plates coated with neurocan or phosphacan. Neurocan and phosphacan inhibited neurite outgrowth from RGCs. The inhibitory effects were derived from the core proteins, not the chondroitin sulfate side chains. The core proteins of neurocan and phosphacan may be inhibitory factors against neurite outgrowth from RGCs during retinal development.
PDGF and Retinal Capillaries
Local metabolic demand regulates retinal blood flow. Models of this autoregulatory process focus on the interplay of molecules that either are vasodilators or vasoconstrictors. Now, based on studies of freshly isolated microvessels, Sakagami et al. (p. 1939) suggest a new mechanism. The authors report that platelet-derived growth factor, which is an endothelial-signaling molecule, serves as a vasoconstrictor when energy supplies are ample and a vasodilator under ischemic conditions. This bifunctional capability links capillary blood flow to metabolic needs. Decreased effectiveness of dual action vasoactive molecules may account for the loss of metabolic autoregulation in the diabetic retina.
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