68-4
30/136

350work cells are exposed to DEX, the extracellular matrix increases and the trabecular meshwork thickens, resulting in an elevation of IOP31). It is also widely known that glucocorticoids affect IOP. However, the relationship between CB function and glucocorticoids remains unclear. We cultured non-pigmented ciliary epithelial cells and found a tendency for adding DEX to reduce the level of Rab8 expression in these cells. Although drugs such as beta-blockers and acetazolamide can alter the production of aqueous humor, we did not observe any changes in the level of Rab8 expres-sion when timolol maleate or acetazolamide was added to cultured CB epithelial cells. We suggest that these proteins influence the function and morphology of the trabecular meshwork. They may also affect the aqueous humor outflow route and thus the IOP. Determining these functions would be relevant for understanding the mecha-nism of IOP control and glaucoma pathogenesis.Although Rab8 might be involved in functions in the CB besides the secretion of aqueous humor, the finding that Rab8 expression in the CB was affected by DEX stimulation indicates that Rab8 may have some effect on IOP dynamics. To obtain more infor-mation on this relationship, analyses of the CB epithelial cell secretome and secreted exosomes and experiments involving co-culture models with trabecular meshwork cells are required. In conclusion, Rab8 probably plays some role in the secretion of aqueous humor in the CB of cyno-molgus monkeys and co-exists with ERM family molecules. Its expression is dependent on stimula-tion by glucocorticoids. Further studies will be needed to investigate the exact role of Rab8 in the CB.AcknowledgmentsNot applicable.No funding was received.Author contributionsKT and IK collected and analyzed the experi-mental date, drafted the manuscript. HO, AC, MA and NS supported the experiment, NE, AM and TI conceived and participated in the study design and critically reviewed the manuscript. 1) Quigley HA, Broman AT: The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol, 2006; 90: 262-267. 2) Quigley HA: Glaucoma. Lancet, 2011; 377: 1367-1377. 3) Kwon YH, Fingert JH, Kuehn MH, Alward WL: Primary open-angle glaucoma. N Engl J Med, 2009; 360: 1113-1124. 4) Goel M, Picciani RG, Lee RK, Bhattacharya SK: Aqueous humor dynamics: a review. Open Ophthalmol J, 2010; 4: 52-59. 5) Coca-Prados M, Escribano J: New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland. Prog Retin Eye Res, 2007; 26: 239-262. 6) Delamere NA: Ciliary Body and Ciliary Epithelium. Adv Organ Biol, 2005; 10: 127-148. 7) Haddad A, Laicine EM, de Almeida JC: Origin and renewal of the intrinsic glycoproteins of the aqueous humor. Graefes Arch Clin Exp Ophthalmol, 1991; 229: 371-379. 8) Vadillo-Ortega F, González-Avila G, Chevez P, Abraham CR, Montaño M, Selman-Lama M: A latent collagenase in human aqueous humor. Invest Ophthalmol Vis Sci, 1989; 30: 332-335. 9) Fautsch MP, Howell KG, Vrabel AM, Charlesworth MC, Muddiman DC, Johnson DH: Primary trabecular meshwork cells incubated in human aqueous humor differ from cells incubated in serum supplements. Invest Ophthalmol Vis Sci, 2005; 46: 2848-2856.10) Kim T, Kim SJ, Kim K, et al: Profiling of vitreous proteomes from proliferative diabetic retinopathy and nondiabetic patients. Proteomics, 2007; 7: 4203-4215.11) García-Ramírez M, Canals F, Hernández C, et al: Proteomic analysis of human vitreous fluid by fluores-cence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy. Diabetologia, 2007; 50: 1294-1303.12) Crabb JW, Miyagi M, Gu X, et al: Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Proc Natl Acad Sci U S A, 2002; 99: 14682-14687.13) Edward DP, Bouhenni R: Anterior segment alterations and comparative aqueous humor proteomics in the buphthalmic rabbit (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc, 2011; 109: 66-114.14) Wang X, Nookala S, Narayanan C, et al: Proteomic analysis of the retina: removal of RPE alters outer segment assembly and retinal protein expression. Glia, 2009; 57: 380-392.15) Okamoto H, Umeda S, Nozawa T, et al: Comparative proteomic analyses of macular and peripheral retina of cynomolgus monkeys (Macaca fascicularis). Exp Anim, 2010; 59: 171-182.16) Yu M, Sun J, Peng W, et al: Protein expression in human trabecular meshwork: downregulation of RhoGDI by The authors declare that there are no conflicts of interest.FundingConflicts of interest statementReferences

元のページ  ../index.html#30

このブックを見る