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| March 2006 | Inside IOVS | Volume 47/3 |
Patterns of Laminin Expression in Ocular Basement Membranes during Development
Defects of different laminin chains (Lns) can cause ocular disease, and therefore a detailed study of the Ln isoforms involved in human ocular development is important to further understand the role of Lns in normal and diseased eyes. Byström et al. (p. 777) show distinct spatial and temporal patterns of distribution for different Lns in the developing human eye structures, suggesting that they have an important role in ocular differentiation. The simultaneous presence of different Lns from the same class in a given basement membrane during development suggests a possible mechanism decreasing the impact of laminin deficiency diseases in the human eye.
Proteomic Analysis of Uveal Melanoma
Zuidervaart et al. (p. 786) demonstrate that proteomic analysis using 2D-PAGE can identify proteins involved in metastasis of uveal melanoma. Most proteins that the authors have characterized are not yet known to be involved in uveal melanoma development. Proteomic analysis, as in this study, can thus provide a clearer insight into the multifactorial mechanisms of uveal melanoma progression. The identification of proteins specifically expressed in uveal melanoma metastases may help to identify biomarkers, leading to earlier identification of liver metastases and thus help to improve survival in uveal melanoma patients with metastatic disease.
Proteomic Analysis of Retinal Pigment Epithelium in Age-Related Macular Degeneration
Limited understanding of the molecular events responsible for age-related macular degeneration (AMD) has constrained the development of effective treatments. Nordgaard et al. (p. 815) employed a proteomics approach to identify proteins exhibiting changes in expression with disease onset and progression in human donor eyes categorized into four progressive stages of AMD. Proteins were identified from several critical pathways that changed at early (protein unfolding, mitochondrial trafficking, regulating apoptosis) and late (regulating retinoic acid, rhodopsin chromophore regeneration) stages, indicating potential causal mechanisms and secondary consequences of AMD, respectively. Their results suggest new directions in AMD research that may ultimately generate novel therapeutic strategies.
Accommodation and Myopia
Accommodative inaccuracy during reading has been presumed to be one of the major risk factors for creating myopia in children. In a longitudinal study of over 1000 school-aged children, investigators in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study (p. 837) show that these inaccuracies during close work occur at the onset of myopia, but not before. This finding suggests that environment may not play as large a role in producing myopia as previously thought. Rather, defocus during reading may be more a consequence rather than a cause of myopia in children.
Activation of the Complement System in Experimental Anterior Autoimmune Uveitis
Idiopathic anterior uveitis is the most common form of intraocular inflammation in humans. Experimental autoimmune anterior uveitis (EAAU) is an organ-specific autoimmune disease of the eye which serves as an animal model of idiopathic human anterior uveitis. Jha et al. (p. 1030) used this model to explore the role of complement in pathogenesis of autoimmune uveitis. Complement is a major component of innate immunity. The authors have demonstrated that the presence and activation of complement system is required for the development of EAAU; deficiency of complement leads to inhibition of EAAU. Thus, inhibition of complement may be a novel therapy for autoimmune uveitis.
Pathways of Antigen Drainage from the Anterior Chamber and the Conjunctiva
Transport of antigen by dendritic cells and drainage of free antigen from peripheral tissues such as the skin to secondary lymphoid organs induces strong antigen-specific immune response. In contrast, antigen placed in the anterior chamber of the eye induces a form of immune tolerance or deviation from immunity. The study by Camelo et al. (p. 1039) examines the migration pathways of antigen from the anterior chamber of the eye to the secondary lymphoid organs. They determined that the bulk of antigen injected into the anterior chamber of the eye reaches the spleen, the lymph nodes of the head and neck and unrelated lymph nodes in a cell-free form via lymphatic and vascular routes. These findings may lead us to reconsider the previously accepted mechanisms proposed to explain tolerance induction following intracameral injections of antigen.
Acanthamoeba Mannose-Binding Protein – A Potential Marker of Pathogenicity
A mannose-based recognition system plays a key role in the amoeba-induced cytopathic effect (CPE). Garate et al. (p. 1056) now show that the pathogenic potential of trophozoites of various Acanthamoeba isolates directly correlates with the expression level of the amoeba mannose-binding protein (MBP). These findings in conjunction with the published studies by the authors showing that Acanthamoeba MBP is a major virulence protein, suggest that the amoeba lectin has the potential to serve as a marker of pathogenicity. This is important because thus far no reliable markers of Acanthamoeba pathogenicity have been described.
Intraocular Lenses That Are Capable of Accommodation
A reduction in the eye's focusing range occurs throughout life, resulting in the need for refractive correction to allow both distance and near objects to be viewed clearly. Cataract surgery removes the hardened crystalline lens inside the eye and replaces it with an intraocular lens (IOL). The study by Wolffsohn et al. (p. 1230) examined the potential for a new type of IOL to restore the focusing ability of the eye. Although the effect was limited and decreased with time after surgery, this study suggests the great potential for IOLs to be modified to allow the restoration of focusing ability in the near future.
Complement Activation in Glaucoma
Complement has been implicated in the pathogenesis of Alzheimer's disease and age-related macular degeneration. The report by Stasi et al. (p. 1024) provides evidence that complement activation may also participate in the pathogenesis of glaucoma. The authors studied the expression of complement component 1q (C1q) in the retina of glaucomatous DBA/2 mice, monkeys with laser induced glaucoma and human archival specimens. Upregulation of C1q mRNA and protein were detected in the DBA/2 mice around the time IOP begins to rise. C1q staining was also detected in glaucomatous monkey eyes and in some (but not all) eyes of glaucomatous patients and was localized to the Muller cells and the area of the inner limiting membrane.
Protection of Retinal Neurons with an Inhibitor of Carbonic Anhydrase
Before cells are irreversibly damaged by diseases which lead to retinal degeneration they undergo a series of changes, among others the cytosolic pH and the DNA content are reduced. In the study by Kniep et al. (p. 1185), the diseases were mimicked by applying apoptosis inducing agents (glyoxal, methylglyoxal, hydrogen peroxide) to cells of a retinal neural cell line. Interestingly, the destructive effects of these agents were alleviated by the carbonic anhydrase blocker dorzolamide. Hence, by blocking carbonic anhydrases and thus preventing an acidification of the cytosol, cells are protected from damage.
Deficiency of SHP-1 Protein-Tyrosine Phosphatase Results in Retinal Degeneration
SHP-1, a protein-tyrosine phosphatase, is a critical negative regulator of signal transduction in hematopoietic cells. The study by Lyons et al. (p. 1201) determined that SHP-1 protein is expressed in the mouse and human retina, and deficiency of this protein in viable motheaten (mev/mev) mice results in a rapidly progressive retinal degeneration. In the retina of mev/mev mice CRALBP is increased and SHP-1 protein is upregulated in the dark-adapted retina, suggesting that SHP-1 may function in visual pigment regeneration. Understanding the mechanism of SHP-1 function in the retina and elucidation of SHP-1 substrates will delineate signaling pathways critical to retinal homeostasis.
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