Objective To investigate the influence of RXRα on refractive development and ocular growth, we used peribulbar injections of selective RXRα agonist and antagonist in normal and form-deprived myopic (FDM) guinea pigs. Methods In this experimental study, 245 3-week-old guinea pigs weighing approximately 100 g were randomly assigned to normal and FD groups. Each group included these subgroups: untreated group, vehicle group and drug-treated group. The vehicle group and drug-treated group received peribulbar injections of DMSO, RXRα agonist Fluorobexarotene and RXRα antagonist HX531 every day for 4 weeks. Refraction and ocular biometric parameters were measured in both eyes of the individual animals before treatment and 2 and 4 weeks after treatment. RXRα expression was detected by immunofluorescence (IF) after all measurements were taken. The results were analyzed with a paired-sample t test and one-way analysis of variance. Results RXRα expression increased after peribulbar injections of RXRα agonist Fluorobexarotene. In addition, the expression of RXRα decreased after RXRα antagonist HX531 treatment. Peribulbar injection of either RXRα agonist Fluorobexarotene or RXRα antagonist HX531 did not result in statistically significant differences in refraction, vitreous chamber or axial length in the normal vision and FDM guinea pigs. Conclusion Peribulbar injection of RXRα agonist Fluorobexarotene and RXRα antagonist HX531 had no significant effect in refractive development and ocular growth in normal and FDM guinea pigs, suggesting that RXRα alone has no direct effect in the regulation of normal refractive development and form deprivation myopia in guinea pigs.
李晓清,柯镜,林俊雄,潘妙珍,瞿佳,周翔天. RXRα对正常及形觉剥夺豚鼠屈光状态及眼球生长的调控[J]. 中华眼视光学与视觉科学杂志, 2016, 18(9): 529-535.
Li Xiaoqing,Ke Jing,Lin Junxiong,Pan Miaozhen,Qu Jia,Zhou Xiangtian. The effect of RXRα on refractive development and ocular growth in normal and form-deprived myopic guinea pigs. Chinese Journal of Optometry Ophthalmology and Visual science, 2016, 18(9): 529-535. DOI: DOI:10.3760/cma.j.issn.1674-845X.2016.09.005
Lam CS, Lam CH, Cheng SC, et al. Prevalence of myopia among Hong Kong Chinese schoolchildren: changes over two decades[J]. Ophthalmic Physiol Opt,2012,32(1):17-24. DOI:10.1111/j.1475-1313.2011.00886.x.
[2]
Sandberg-Lall M, Hagg PO, Wahlstrom I, et al. Type XIII collagen is widely expressed in the adult and developing human eye and accentuated in the ciliary muscle, the optic nerve and the neural retina[J]. Exp Eye Res,2000,70(4):401-410. DOI:10. 1006/exer.1998.0826.
[3]
Siegwart JT Jr, Norton TT. Regulation of the mechanical properties of tree shrew sclera by the visual environment[J]. Vision Res,1999,39(2):387-407.
[4]
Phillips JR, Khalaj M, McBrien NA. Induced myopia associated with increased scleral creep in chick and tree shrew eyes[J]. Invest Ophthalmol Vis Sci,2000,41(8):2028-2034.
[5]
Goodman DS. Vitamin A and retinoids in health and disease[J]. N Engl J Med,1984,310(16):1023-1031. DOI:10.1056/NEJM1984 04193101605.
[6]
Sporn MB, Roberts AB. Role of retinoids in differentiation and carcinogenesis[J]. J Natl Cancer Inst,1984,73(6):1381-1387.
[7]
Wang Z, Xu J, Zheng Y, et al. Effect of the regulation of retinoid X receptor-alpha gene expression on rat hepatic fibrosis[J]. Hepatol Res,2011,41(5):475-483. DOI:10.1111/j.1872-034X.2011.00794.x.
Li C, McFadden SA, Morgan I, et al. All-trans retinoic acid regulates the expression of the extracellular matrix protein fibulin-1 in the guinea pig sclera and human scleral fibroblasts[J]. Mol Vis,2010,16:689-697.
[10]
Bugge TH, Pohl J, Lonnoy O, et al. RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors[J]. EMBO J,1992,11(4):1409-1418.
[11]
Kliewer SA, Umesono K, Mangelsdorf DJ. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling[J]. Nature,1992,355(6359):446-449. DOI:10.1038/355446a0.
[12]
Gearing KL, Gottlicher M, Teboul M, et al. Interaction of the peroxisome-proliferator-activated receptor and retinoid X receptor[J]. Proc Natl Acad Sci USA,1993,90(4):1440-1444.
[13]
Szanto A, Narkar V, Shen Q, et al. Retinoid X receptors: X-ploring their (patho) physiological functions[J]. Cell Death Differ,2004,11 Suppl 2:S126-S143. DOI:10.1038/sj.cdd.4401533.
[14]
Ohata M, Lin M, Satre M, et al. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis[J]. Am J Physiol,1997,272(3 Pt 1):G589-596.
[15]
Rankin AC, Hendry BM, Corcoran JP, et al. An in vitro model for the pro-fibrotic effects of retinoids: mechanisms of action[J]. Br J Pharmacol,2013,170(6):1177-1189. DOI:10.1111/bph.12348.
[16]
Redlich CA, Delisser HM, Elias JA. Retinoic acid inhibition of transforming growth factor-beta-induced collagen production by human lung fibroblasts[J]. Am J Respir Cell Mol Biol,1995,12(3):287-295. DOI:10.1165/ajrcmb.12.3.7873195.
[17]
Kastner P, Grondona JM, Mark M, et al. Genetic analysis of RXR alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis[J]. Cell,1994,78(6):987-1003.
[18]
Mascrez B, Ghyselinck NB, Chambon P, et al. A transcriptionally silent RXRalpha supports early embryonic morphogenesis and heart development[J]. Proc Natl Acad Sci USA,2009,106(11): 4272-4277. DOI:10.1073/pnas.0813143106.
[19]
Rada JA, Shelton S, Norton TT, et al. The sclera and myopia[J]. Exp Eye Res,2006,82(2):185-200. DOI:10.1016/j.exer.2005. 08.009.
[20]
Dong F, Zhi Z, Pan M, et al. Inhibition of experimental myopia by a dopamine agonist: different effectiveness between form deprivation and hyperopic defocus in guinea pigs[J]. Mol Vis, 2011,17:2824-2834.
[21]
Li M, Yuan Y, Chen Q, et al. Expression of Wnt/beta-Catenin Signaling Pathway and Its Regulatory Role in Type I Collagen with TGF-beta1 in Scleral Fibroblasts from an Experimentally Induced Myopia Guinea Pig Model[J]. J Ophthalmol,2016,2016:5126560. DOI:10.1155/2016/5126560.
[22]
McFadden SA, Howlett MH, Mertz JR. Retinoic acid signals the direction of ocular elongation in the guinea pig eye[J]. Vision Res,2004,44(7):643-653.
[23]
Troilo D, Nickla DL, Mertz JR, et al. Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets[J]. Invest Ophthalmol Vis Sci,2006,47(5):1768-1777. DOI:10.1167/iovs.05-0298.
[24]
McFadden SA, Howlett MH, Mertz JR, et al. Acute effects of dietary retinoic acid on ocular components in the growing chick[J]. Exp Eye Res,2006,83(4):949-961. DOI:10.1016/j.exer.2006.05. 002.
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