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oa Editorial [Hot topic: Molecular Ophthalmology (Guest Editor: David W. Li)]
- Source: Current Molecular Medicine, Volume 10, Issue 9, Dec 2010, p. 774 - 775
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- 01 Dec 2010
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Abstract
Some years ago, I attended a research conference on the macular degeneration in the John Hopkins Medical Center where I obtained a set of textbooks named ‘Principles and Practice of Ophthalmology (second edition)’ by Daniel A. Albert and Frederick A. Jakobiec. Of 6 volumes, the longest one deals with the basic sciences of ophthalmology, which contains over 1400 pages in 119 chapters by over 150 authors. If you have read this textbook and are invited to edit a special issue about molecular ophthalmology with just a few articles, you may wonder what to do with such extensive topics as I did in the beginning. Nevertheless, the eye is a beautiful organ and ocular diseases greatly affect our health. Thus, this special edition of Current Molecular Medicine contains the review articles on the pathology, the related mechanism and the possible management of the major ocular diseases. Seven articles have been selected to cover retinal pigment epithelium and retinal diseases, glaucoma and treatment, cataractogenesis derived from changes in lens structural proteins, gap junctions or cell death, and corneal disease therapy by limbal stem cells. The small heat shock proteins (sHsps) have extremely important roles in the eye. Among the 11 different sHsps, αA/B-crystallins are lens structural proteins. These two and also Hsp27 are expressed in three major compartments (retina, lens and cornea) of the eye where they perform both structural and non-structural roles. The article by Arrigo and Simon reviewed the functions of these sHsps in the eye. After a brief discussion on their developmental expression, the authors gave a detailed description of these sHsps in acting as chaperones, anti-oxidative components and anti-apoptotic regulators. Then, the authors discussed various mutations and functional changes of the three major sHsps that lead to cataractogenesis, corneal and retinal pathogenesis. Finally, the authors suggested the potential using sHsps for ocular disease therapy. This is one of the most comprehensive reviews about the roles of sHsps in ocular diseases. SUMOylation is a post-translation process in which various substrate proteins such as transcriptional factors and signaling molecules are modified by addition of a single SUMO peptide (SUMO 1) or multiple copies of SUMO peptides (2 and 3). The discovery of this posttranslational modification came to the stage about a decade ago. The article by Gong and Li provided an updated review regarding the functions of SUMOylation in the eye. SUMOylation plays a very important role in regulating the differentiation of both retina and lens. In this article, the authors summarized the functions of SUMOylation in modulating two important transcription factors, Nr2e3 and Nrl, which regulate differentiation of rods and cones in the retina. They further discussed the function modification of the p32 Pax-6 by SUMOylation, which turns on both DNA binding and transcription activation. Finally, the authors discussed the modification of the surviving factor, Ledgf, by SUMOylation and the possible role of this modification. Photo-transduction is the major functional process of the eye. During this process, the retinal pigment epithelium plays an indispensable role. The article by Sparrow et al. provided an updated review about the retinal pigment epithelium in normal health and diseases. The author first described the structural features of the retinal pigment epithelial cells (RPE), and its functional importance related to photo-transduction by the photoreceptor cells (PR). Then, the author discussed the major functions of RPE in conversion and storage of retinoid, the phagocytosis of shed PR outer segment membrane, the absorption of scattered light, ion and fluid transport and RPE-PR apposition, and the primary dysfunctioning of the RPE in visual cell death and blindness. Glaucoma is a syndrome derived from optic nerve damage, and progressive and irreversible loss of vision, which is likely due to increased intraocular pressure. The article by Toris reviewed the basis for this disease and also its treatment. The author first discussed the aqueous humor dynamics, which determines the intraocular pressure. Then, the author described the three types of drugs used for glaucoma treatment: those suppressing aqueous facility, those enhancing aqueous facility and those having both suppressing and enhancing effects, and provided an updated review on glaucoma therapy by these different drugs. A transparent cornea is essential for reflecting light into the eye. The article by Tseng et al. discussed how to use the limbal epithelial stem cells for treatment of human corneal diseases. After a brief recall of the historical background regarding limbal epithelial stem cell study, the authors gave a critical appraisal about the current protocols used for ex vivo expansion of human limbal epithelial cells and indicated the potential pitfalls in each of the six protocols. The authors finally concluded that the major aspect one can improve regarding ex vivo expansion of human limbal epithelial cells is how to develop the surrogate feeder layers more like the native limbal niche environment. Gap junctions are important membrane channels mediating direct cell-cell communication in multicellular organisms. The article by Jiang et al. provided a comprehensive review about the hemi-channels and gap junctions derived from two types of junction proteins: Cx46 and Cx50 in the ocular lens. The author first described their expression in lens fiber cells, the various types of mutations across different domains of connexin molecules and the genetic deletion of the two genes related to development of cataracts. The author further discussed the differential functions of Cx46 and Cx50 in lens cell growth and development and suggested that the function of Cx50 in epithelial-fiber differentiation appears to be derived from its non-conventional role. Finally, the author suggested that connexin molecules might be potential drug targets for therapeutic intervention for the treatment of cataracts and other eye disorders. Lens cataract is derived from genetic mutations (congenital cataract), aging or lens damage induced by various stress conditions (non-congenital cataract). The article by Zhang et al. summarized the current knowledge about the functions of both developmental apoptosis in the embryonic lens and stress-induced apoptosis in the adult lens, and discussed the close relationships between induced apoptosis and microphthalmia and/or cataractogenesis. The authors also reviewed the major regulators controlling apoptosis in the ocular lens. In summary, this special issue touches aspects of the comprehensive vision science field. It is our intention to give the readers both a general overview on the topic selected and also specific advance in that field covered. ACKNOWLEDGEMENTS I thank the financial support from the National Eye Institute/ National Institutes of Health (EY018380 and EY015765) and other organizations including the University of Nebraska Medical Center, the University of Minnesota Graduate School, the New Jersey Foundation, and the Lotus Scholar Program from the Ministry of Hunan Province Government and Hunan Normal University.