[New understanding and development of medical treatments for ocular diseases based upon molecular mechanisms].
A number of genes associated with life phenomena have been identified by the achievement of genome projects. As both comprehensive analysis and methods for investigation of specific genes have been developed, we can understand the pathogenesis of ocular diseases and develop novel medical treatments based upon detailed information on molecular mechanisms. In our review article, we focused on three vision-threatening ocular diseases; glaucoma, age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR), and discussed the potential and problems related to retinal regenerative therapy. Regarding glaucoma, we investigated the relationships between aqueous humor and cell components in the aqueous outflow route. We have revealed that the Rho-Rho-associated coiled-coil-forming protein kinase (ROCK) signal transduction pathway participates in regulation of the aqueous outflow route, and that ROCK inhibitors and several protein kinase inhibitors exert intraocular pressure-lowering effects. Also, we conducted a series of investigations on familial amyloidotic polyneuropathy (FAP), as a representative secondary glaucoma caused by genetic mutations in a single gene. We reviewed the clinical features of ocular complications derived from FAP, their molecular mechanisms and possibilities for the development of novel medical treatments. In addition, we discussed a novel therapeutic concept, "neuroprotection", and showed the potential of some drugs as candidates for the neuroprotective treatment of glaucoma. Against AMD, we have performed a series of experiments from the viewpoint of similarity with atherosclerotic lesions. We have shown the molecular mechanisms of AMD associated with up-regulated expression of scavenger receptors and the interaction between leukocytes and vascular endothelial cells. Furthermore, in the pathogenesis of PVR, we described the role of epithelial-mesenchymal transition in retinal pigment epithelial cells and demonstrated the usefulness of enzymatic vitrectomy. Although retinal regenerative therapy has attracted much attention from global investigators, we pointed out its limitation for clinical application, and developed researches on efficient culture method using physiologically active factors for proliferating retinal stem cells with multi-potentiality, differentiation of the transplanted progenitor cells, and axon guidance of neurons by extracellular matrices.
Tanihara
Hidenobu
H
Department of Ophthalmology & Visual Science, Kumamoto University Graduate School of Medical Sciences, Japan.
D000818:Animals; D015195:Drug Design; D005901:Glaucoma / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000628:therapy*; D008967:Molecular Biology; D039902:Multipotent Stem Cells; D009154:Mutation; D044968:Regenerative Medicine; D012160:Retina / Q000166:cytology / Q000502:physiology; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics* / Q000628:therapy*