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| February 2008 | Inside IOVS | Volume 49/2 |
Tissue Transglutaminase (TGM2) and the Human Trabecular Meshwork
In the glaucomatous trabecular meshwork (TM) there is increased accumulation of extracellular matrix (ECM) material due to a disruption of the normal balance between ECM deposition and degradation. TGM2 is known to catalyze the post-translational modification of proteins via formation of isopeptide bonds which become highly resistant to enzymatic degradation. In this study, Tovar-Vidales et al. (p. 622) focused on the differences between normal and glaucomatous TM and demonstrated increased TGM2 protein expression and activity in both glaucomatous human TM cells and tissues. Thus, this report provides evidence that TGM2 may play a role in glaucomatous damage to the TM.
Increased Susceptibility to Form Deprivation Myopia in a Mouse Model
Patients with the complete form of congenital stationary night blindness (CSNB1), which is associated with a retinal ON pathway defect, present with high myopia. This study explores the role of ON pathway transmission and dopamine in refractive development by examining nob mice, a model of CSNB1. Pardue et al. (p. 706) found that refractive development under normal laboratory conditions was similar between nob and wild-type mice, although nob mice had lower dopamine levels. However, with the application of form depriving goggles, the nob mice produced a larger and more rapid myopic shift than did WT mice. The results support the hypothesis that interactions between genetic and environmental factors influence the susceptibility to myopia.
Erythropoietin Protects Retinal Cells in Diabetes
Erythropoietin (EPO) introduced into the vitreous prevents programmed cell death and maintains the integrity of the blood-retinal barrier early in the course of diabetes. Zhang et al. (p. 732) showed that upregulation of the EPO receptor acts as a maintenance/survival mechanism in retinal neurons responding to early diabetic insults other than ischemia. They demonstrate the protective function of EPO, which acts in part through the ERK-dependent pathway. This work suggests a promising therapeutic approach in the prevention of retinal cell death in early diabetic retinopathy.
Abnormally Elevated Lysosomal pH and Defective RPE Function
The lysosomal enzymes of RPE cells that degrade engulfed photoreceptor outer segments function best within a narrow range of acidic pH values. Liu et al. (p. 772) demonstrate an elevated lysosomal pH both in RPE cells from ABCA4-/- mice and in ARPE-19 cells treated with N-retinylidene-N-retinylethanolamine (A2E). Pharmacological approaches to reacidify compromised lysosomes identified with high-throughput methods are effective even in adult ABCA4-/- mice. Moreover, the enhancement of outer segment clearance suggests that restoration of lysosomal acidity may limit the accumulation of lipofuscin-like debris of outer segment origin in disorders associated with impaired lysosomal activity in RPE cells.
Functional Connexin43 Channels Protect against Oxidative Stress
Age-related macular degeneration (AMD) is a common cause of irreversible blindness in aging individuals. Disruption of the monolayer integrity of the retinal pigment epithelium (RPE) is an essential and necessary pathological event in this disease. Hutnik et al. (p. 800) show that functional Connexin43 channels have a protective role when a cell line of human RPE cells are exposed to oxidative stress, the latter of which has been implicated in the pathogenesis of AMD. In the future, agents targeting gap junctions may be considered in the treatment and/or prevention of this condition.
Optimal Twilight Color Vision Requires Adequate Retinal Oxygen
Connolly et al. (p. 820) show that the suggestion that outer retinal function may be increasingly vulnerable to exogenous hypoxia with decreasing light, as rod oxygen consumption increases, is supported by an effect of mild hypoxia to impair threshold chromatic sensitivity progressively with decreasing mesopic luminance. The findings support a role of hypoxia in the aetiology of disease-induced tritan defects, suggest consistent binocular summation of chromatic signals (independently of the luminance channel), and are relevant to aircrew visual performance during night flying at modest altitudes. The City University Colour Assessment and Diagnosis (CAD) test is highly sensitive to mild color losses at photopic and mesopic luminance.
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