The role of retinal signaling molecules in the occurrence and progression of myopia_Chinese Journal of Ocular Fundus Diseases

Authors：

Liu Nianen , Liu Siyi ,  Zhang Yan

Tianjin Medical University Eye Hospital, School of Optometry and Eye Institute, Tianjin Branch of National Clinical Research Center for Ocular Diseases, Tianjin Key Laboratory of Retinal Function and Diseases, Tianjin 300384, China;

Corresponding author：

Zhang Yan, Email: yanzhang04@tmu.edu.cn

Keywords：

Myopia; Retina; Pathogenesis; Scleral hypoxia theory; Targets; Review

DOI：

10.3760/cma.j.cn511434-20220209-00074

Video：

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Abstract Full text Figures/Tables Video References Cited by

With the surged prevalence of myopia, the pathogenic mechanism underlying myopia has attracted attention. At present, it is generally believed in the flied that the reduced blood perfusion in the choroid is crucial for myopigenesis. Then, in the process of myopigenesis, how are the blurred visual signals transmitted to the choroidal blood vessels through the retina and retinal pigment epithelium, leading to the reduced choroidal blood perfusion. The cellular and molecular mechanisms underpinning this process remain elusive. In recent years, the theory of scleral hypoxia has attracted much attention. Popular signaling molecules in current research include dopamine, epidermal growth factor, retinoic acid, cholinergic molecules and adenosine, etc. These factors are likely to participate in signal transduction in retina and RPE, thus causing changes in choroidal blood flow and affecting the occurrence and development of myopia. Therefore, these signaling factors and their downstream pathways may provide new ideas for the prevention and control of myopia targets.

Citation： Liu Nianen, Liu Siyi, Zhang Yan. The role of retinal signaling molecules in the occurrence and progression of myopia. Chinese Journal of Ocular Fundus Diseases, 2023, 39(8): 696-700. doi: 10.3760/cma.j.cn511434-20220209-00074 Copy

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2.	Wu H, Chen W, Zhao F, et al. Scleral hypoxia is a target for myopia control[J/OL]. Proc Natl Acad Sci USA, 2018, 115(30): E7091-7100[2018-07-24]. https://pubmed.ncbi.nlm.nih.gov/29987045/. DOI: 10.1073/pnas.1721443115.
3.	Nickla DL, Wildsoet C, Wallman J. Compensation for spectacle lenses involves changes in proteoglycan synthesis in both the sclera and choroid[J]. Curr Eye Res, 1997, 16(4): 320-326. DOI: 10.1076/ceyr.16.4.320.10697.
4.	Pendrak K, Papastergiou GI, Lin T, et al. Choroidal vascular permeability in visually regulated eye growth[J]. Exp Eye Res, 2000, 70(5): 629-637. DOI: 10.1006/exer.2000.0825.
5.	Hirata A, Negi A. Morphological changes of choriocapillaris in experimentally induced chick myopia[J]. Graefe's Arch Clin Exp Ophthalmol, 1998, 236(2): 132-137. DOI: 10.1007/s004170050053.
6.	Rymer J, Wildsoet CF. The role of the retinal pigment epithelium in eye growth regulation and myopia: a review[J]. Vis Neurosci, 2005, 22(3): 251-261. DOI: 10.1017/s0952523805223015.
7.	Nickla DL, Wallman J. The multifunctional choroid[J]. Prog Retin Eye Res, 2010, 29(2): 144-168. DOI: 10.1016/j.preteyeres.2009.12.002.
8.	Zou L, Liu R, Zhang X, et al. Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model[J]. Mol Vis, 2014, 20: 977-987.
9.	Wallman J, Gottlieb MD, Rajaram V, et al. Local retinal regions control local eye growth and myopia[J]. Science, 1987, 237(4810): 73-77. DOI: 10.1126/science.3603011.
10.	Zhou X, Pardue MT, Iuvone PM, et al. Dopamine signaling and myopia development: What are the key challenges[J]. Prog Retin Eye Res, 2017, 61: 60-71. DOI: 10.1016/j.preteyeres.2017.06.003.
11.	Huang F, Wang Q, Yan T, et al. The role of the dopamine D2 receptor in form-deprivation myopia in mice: studies with full and partial D2 receptor agonists and knockouts[J]. Invest Ophthalmol Vis Sci, 2020, 61(6): 47. DOI: 10.1167/iovs.61.6.47.
12.	Nickla DL, Totonelly K, Dhillon B. Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks[J]. Exp Eye Res, 2010, 91(5): 715-720. DOI: 10.1016/j.exer.2010.08.021.
13.	董枫, 安建宏, 任岳萍, 等. 多巴胺D2受体和腺苷A2A受体在人视网膜色素上皮细胞表达的研究[J]. 中华眼科杂志, 2007, 43(12): 1110-1113. DOI: 10.3760/j.issn:0412-4081.2007.12.013.Dong F, An JH, Ren YP, et al. Expression of dopamine receptor D2 and adenosine receptor A2A in human retinal pigment epithelium[J]. Chin J Ophthalmol, 2007, 43(12): 1110-1113. DOI: 10.3760/j.issn:0412-4081.2007.12.013.
14.	Kimura R, Okouchi M, Kato T, et al. Epidermal growth factor receptor transactivation is necessary for glucagon-like peptide-1 to protect PC12 cells from apoptosis[J]. Neuroendocrinology, 2013, 97(4): 300-308. DOI: 10.1159/000345529.
15.	Yoon S, Baik JH. Dopamine D2 receptor-mediated epidermal growth factor receptor transactivation through a disintegrin and metalloprotease regulates dopaminergic neuron development via extracellular signal-related kinase activation[J]. J Biol Chem, 2013, 288(40): 28435-28446. DOI: 10.1074/jbc.M113.461202.
16.	Jonas JB, Dong L, Da Chen S, et al. Intraocular epidermal growth factor concentration, axial length, and high axial myopia[J]. Graefe's Arch Clin Exp Ophthalmol, 2021, 259(11): 3229-3234. DOI: 10.1007/s00417-021-05200-5.
17.	Dong L, Shi XH, Li YF, et al. Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia[J]. FASEB J, 2020, 34(10): 13654-13670. DOI: 10.1096/fj.202001095RR.
18.	Jonas JB, Ohno-Matsui K, Jiang WJ, et al. Bruch membrane and the mechanism of myopization: a new theory[J]. Retina, 2017, 37(8): 1428-1440. DOI: 10.1097/iae.0000000000001464.
19.	Jonas JB, Ohno-Matsui K, Holbach L, et al. Retinal pigment epithelium cell density in relationship to axial length in human eyes[J/OL]. Acta Ophthalmol, 2017, 95(1): e22-e28[2016-08-22].https://pubmed.ncbi.nlm.nih.gov/27545271/. DOI: 10.1111/aos.13188.
20.	Yu M, Liu W, Wang B, et al. Short wavelength (blue) light is protective for lens-induced myopia in guinea pigs potentially through a retinoic acid-related mechanism[J]. Invest Ophthalmol Vis Sci, 2021, 62(1): 21. DOI: 10.1167/iovs.62.1.21.
21.	Summers JA, Cano EM, Kaser-Eichberger A, et al. Retinoic acid synthesis by a population of choroidal stromal cells[J/OL]. Exp Eye Res, 2020, 201: 108252[2020-09-19].https://pubmed.ncbi.nlm.nih.gov/32961175/. DOI: 10.1016/j.exer.2020.108252.
22.	Rada JA, Hollaway LR, Lam W, et al. Identification of RALDH2 as a visually regulated retinoic acid synthesizing enzyme in the chick choroid[J]. Invest Ophthalmol Vis Sci, 2012, 53(3): 1649-1662. DOI: 10.1167/iovs.11-8444.
23.	Wang S, Liu S, Mao J, et al. Effect of retinoic acid on the tight junctions of the retinal pigment epithelium-choroid complex of guinea pigs with lens-induced myopia in vivo[J]. Int J Mol Med, 2014, 33(4): 825-832. DOI: 10.3892/ijmm.2014.1651.
24.	Satoh T, Higuchi Y, Kawakami S, et al. Encapsulation of the synthetic retinoids Am80 and LE540 into polymeric micelles and the retinoids' release control[J]. J Control Release, 2009, 136(3): 187-195. DOI: 10.1016/j.jconrel.2009.02.024.
25.	Ruan Y, Patzak A, Pfeiffer N, et al. Muscarinic acetylcholine receptors in the retina-therapeutic implications[J/OL]. Int J Mol Sci, 2021, 22(9): 4989[2021-05-09].https://pubmed.ncbi.nlm.nih.gov/34066677/. DOI: 10.3390/ijms22094989.
26.	Gong Q, Janowski M, Luo M, et al. Efficacy and adverse effects of atropine in childhood myopia: a meta-analysis[J]. JAMA Ophthalmol, 2017, 135(6): 624-630. DOI: 10.1001/jamaophthalmol.2017.1091.
27.	Lind GJ, Chew SJ, Marzani D, et al. Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes[J]. Invest Ophthalmol Vis Sci, 1998, 39(12): 2217-2231.
28.	Barathi VA, Beuerman RW. Molecular mechanisms of muscarinic receptors in mouse scleral fibroblasts: prior to and after induction of experimental myopia with atropine treatment[J/OL]. Mol Vis, 2011, 17: 680-692[2011-03-09]. https://pubmed.ncbi.nlm.nih.gov/21403852/.
29.	Lin HJ, Wan L, Chen WC, et al. Muscarinic acetylcholine receptor 3 is dominant in myopia progression[J]. Invest Ophthalmol Vis Sci, 2012, 53(10): 6519-6525. DOI: 10.1167/iovs.11-9031.
30.	Stone RA, Lin T, Laties AM. Muscarinic antagonist effects on experimental chick myopia[J]. Exp Eye Res, 1991, 52(6): 755-758. DOI: 10.1016/0014-4835(91)90027-c.
31.	Cottriall CL, McBrien NA. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew[J]. Invest Ophthalmol Vis Sci, 1996, 37(7): 1368-1379.
32.	Cottriall CL, Truong HT, McBrien NA. Inhibition of myopia development in chicks using himbacine: a role for M(4) receptors?[J]. Neuroreport, 2001, 12(11): 2453-2456. DOI: 10.1097/00001756-200108080-00033.
33.	McBrien NA, Arumugam B, Gentle A, et al. The M4 muscarinic antagonist MT-3 inhibits myopia in chick: evidence for site of action[J]. Ophthalmic Physiol Opt, 2011, 31(5): 529-539. DOI: 10.1111/j.1475-1313.2011.00841.x.
34.	McBrien NA, Stell WK, Carr B. How does atropine exert its anti-myopia effects?[J]. Ophthalmic Physiol Opt, 2013, 33(3): 373-378. DOI: 10.1111/opo.12052.
35.	Arumugam B, McBrien NA. Muscarinic antagonist control of myopia: evidence for M4 and M1 receptor-based pathways in the inhibition of experimentally-induced axial myopia in the tree shrew[J]. Invest Ophthalmol Vis Sci, 2012, 53(9): 5827-5837. DOI: 10.1167/iovs.12-9943.
36.	Nickla DL, Zhu X, Wallman J. Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning[J]. Ophthalmic Physiol Opt, 2013, 33(3): 245-256. DOI: 10.1111/opo.12054.
37.	张立华, 闫东升, 周翔天, 等. 毒蕈碱1型受体在人视网膜色素上皮细胞表达的研究[J]. 中华眼科杂志, 2006, 42(12): 1109-1112. DOI: 10.3760/j:issn:0412-4081.2006.12.011.Zhang LH, Yan DS, Zhou XT, et al. Expression of muscarinic acetylcholine receptor-1 in human retinal pigment epithelium[J]. Chin J Ophthalmol, 2006, 42(12): 1109-1112. DOI: 10.3760/j:issn:0412-4081.2006.12.011.
38.	Beach KM, Hung LF, Arumugam B, et al. Adenosine receptor distribution in rhesus monkey ocular tissue[J]. Exp Eye Res, 2018, 174: 40-50. DOI: 10.1016/j.exer.2018.05.020.
39.	Cui D, Trier K, Zeng J, et al. Adenosine receptor protein changes in guinea pigs with form deprivation myopia[J]. Acta Ophthalmol, 2010, 88(7): 759-765. DOI: 10.1111/j.1755-3768.2009.01559.x.
40.	Cui D, Trier K, Zeng J, et al. Effects of 7-methylxanthine on the sclera in form deprivation myopia in guinea pigs[J]. Acta Ophthalmol, 2011, 89(4): 328-334. DOI: 10.1111/j.1755-3768.2009.01688.x.
41.	Walline JJ, Lindsley KB, Vedula SS, et al. Interventions to slow progression of myopia in children[J/OL]. Cochrane Database Syst Rev, 2020, 1(1): CD004916[2020-01-13]. https://pubmed.ncbi.nlm.nih.gov/31930781/. DOI: 10.1002/14651858.CD004916.pub4.
42.	Smith EL 3rd, Hung LF, She Z, et al. Topically instilled caffeine selectively alters emmetropizing responses in infant rhesus monkeys[J/OL]. Exp Eye Res, 2021, 203: 108438[2021/01/09]. https://pubmed.ncbi.nlm.nih.gov/33428866/. DOI: 10.1016/j.exer.2021.108438.
43.	Liu H, Schaeffel F, Trier K, et al. Effects of 7-methylxanthine on deprivation myopia and retinal dopamine release in chickens[J]. Ophthalmic Res, 2020, 63(3): 347-357. DOI: 10.1159/000502529.

1. Baird PN, Saw SM, Lanca C, et al. Myopia[J/OL]. Nat Rev Dis Primers, 2020, 6(1): 99[2020/12/17]. https://pubmed.ncbi.nlm.nih.gov/33328468/. DOI: 10.1038/s41572-020-00231-4.
2. Wu H, Chen W, Zhao F, et al. Scleral hypoxia is a target for myopia control[J/OL]. Proc Natl Acad Sci USA, 2018, 115(30): E7091-7100[2018-07-24]. https://pubmed.ncbi.nlm.nih.gov/29987045/. DOI: 10.1073/pnas.1721443115.
3. Nickla DL, Wildsoet C, Wallman J. Compensation for spectacle lenses involves changes in proteoglycan synthesis in both the sclera and choroid[J]. Curr Eye Res, 1997, 16(4): 320-326. DOI: 10.1076/ceyr.16.4.320.10697.
4. Pendrak K, Papastergiou GI, Lin T, et al. Choroidal vascular permeability in visually regulated eye growth[J]. Exp Eye Res, 2000, 70(5): 629-637. DOI: 10.1006/exer.2000.0825.
5. Hirata A, Negi A. Morphological changes of choriocapillaris in experimentally induced chick myopia[J]. Graefe's Arch Clin Exp Ophthalmol, 1998, 236(2): 132-137. DOI: 10.1007/s004170050053.
6. Rymer J, Wildsoet CF. The role of the retinal pigment epithelium in eye growth regulation and myopia: a review[J]. Vis Neurosci, 2005, 22(3): 251-261. DOI: 10.1017/s0952523805223015.
7. Nickla DL, Wallman J. The multifunctional choroid[J]. Prog Retin Eye Res, 2010, 29(2): 144-168. DOI: 10.1016/j.preteyeres.2009.12.002.
8. Zou L, Liu R, Zhang X, et al. Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model[J]. Mol Vis, 2014, 20: 977-987.
9. Wallman J, Gottlieb MD, Rajaram V, et al. Local retinal regions control local eye growth and myopia[J]. Science, 1987, 237(4810): 73-77. DOI: 10.1126/science.3603011.
10. Zhou X, Pardue MT, Iuvone PM, et al. Dopamine signaling and myopia development: What are the key challenges[J]. Prog Retin Eye Res, 2017, 61: 60-71. DOI: 10.1016/j.preteyeres.2017.06.003.
11. Huang F, Wang Q, Yan T, et al. The role of the dopamine D2 receptor in form-deprivation myopia in mice: studies with full and partial D2 receptor agonists and knockouts[J]. Invest Ophthalmol Vis Sci, 2020, 61(6): 47. DOI: 10.1167/iovs.61.6.47.
12. Nickla DL, Totonelly K, Dhillon B. Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks[J]. Exp Eye Res, 2010, 91(5): 715-720. DOI: 10.1016/j.exer.2010.08.021.
13. 董枫, 安建宏, 任岳萍, 等. 多巴胺D2受体和腺苷A2A受体在人视网膜色素上皮细胞表达的研究[J]. 中华眼科杂志, 2007, 43(12): 1110-1113. DOI: 10.3760/j.issn:0412-4081.2007.12.013.Dong F, An JH, Ren YP, et al. Expression of dopamine receptor D2 and adenosine receptor A2A in human retinal pigment epithelium[J]. Chin J Ophthalmol, 2007, 43(12): 1110-1113. DOI: 10.3760/j.issn:0412-4081.2007.12.013.
14. Kimura R, Okouchi M, Kato T, et al. Epidermal growth factor receptor transactivation is necessary for glucagon-like peptide-1 to protect PC12 cells from apoptosis[J]. Neuroendocrinology, 2013, 97(4): 300-308. DOI: 10.1159/000345529.
15. Yoon S, Baik JH. Dopamine D2 receptor-mediated epidermal growth factor receptor transactivation through a disintegrin and metalloprotease regulates dopaminergic neuron development via extracellular signal-related kinase activation[J]. J Biol Chem, 2013, 288(40): 28435-28446. DOI: 10.1074/jbc.M113.461202.
16. Jonas JB, Dong L, Da Chen S, et al. Intraocular epidermal growth factor concentration, axial length, and high axial myopia[J]. Graefe's Arch Clin Exp Ophthalmol, 2021, 259(11): 3229-3234. DOI: 10.1007/s00417-021-05200-5.
17. Dong L, Shi XH, Li YF, et al. Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia[J]. FASEB J, 2020, 34(10): 13654-13670. DOI: 10.1096/fj.202001095RR.
18. Jonas JB, Ohno-Matsui K, Jiang WJ, et al. Bruch membrane and the mechanism of myopization: a new theory[J]. Retina, 2017, 37(8): 1428-1440. DOI: 10.1097/iae.0000000000001464.
19. Jonas JB, Ohno-Matsui K, Holbach L, et al. Retinal pigment epithelium cell density in relationship to axial length in human eyes[J/OL]. Acta Ophthalmol, 2017, 95(1): e22-e28[2016-08-22].https://pubmed.ncbi.nlm.nih.gov/27545271/. DOI: 10.1111/aos.13188.
20. Yu M, Liu W, Wang B, et al. Short wavelength (blue) light is protective for lens-induced myopia in guinea pigs potentially through a retinoic acid-related mechanism[J]. Invest Ophthalmol Vis Sci, 2021, 62(1): 21. DOI: 10.1167/iovs.62.1.21.
21. Summers JA, Cano EM, Kaser-Eichberger A, et al. Retinoic acid synthesis by a population of choroidal stromal cells[J/OL]. Exp Eye Res, 2020, 201: 108252[2020-09-19].https://pubmed.ncbi.nlm.nih.gov/32961175/. DOI: 10.1016/j.exer.2020.108252.
22. Rada JA, Hollaway LR, Lam W, et al. Identification of RALDH2 as a visually regulated retinoic acid synthesizing enzyme in the chick choroid[J]. Invest Ophthalmol Vis Sci, 2012, 53(3): 1649-1662. DOI: 10.1167/iovs.11-8444.
23. Wang S, Liu S, Mao J, et al. Effect of retinoic acid on the tight junctions of the retinal pigment epithelium-choroid complex of guinea pigs with lens-induced myopia in vivo[J]. Int J Mol Med, 2014, 33(4): 825-832. DOI: 10.3892/ijmm.2014.1651.
24. Satoh T, Higuchi Y, Kawakami S, et al. Encapsulation of the synthetic retinoids Am80 and LE540 into polymeric micelles and the retinoids' release control[J]. J Control Release, 2009, 136(3): 187-195. DOI: 10.1016/j.jconrel.2009.02.024.
25. Ruan Y, Patzak A, Pfeiffer N, et al. Muscarinic acetylcholine receptors in the retina-therapeutic implications[J/OL]. Int J Mol Sci, 2021, 22(9): 4989[2021-05-09].https://pubmed.ncbi.nlm.nih.gov/34066677/. DOI: 10.3390/ijms22094989.
26. Gong Q, Janowski M, Luo M, et al. Efficacy and adverse effects of atropine in childhood myopia: a meta-analysis[J]. JAMA Ophthalmol, 2017, 135(6): 624-630. DOI: 10.1001/jamaophthalmol.2017.1091.
27. Lind GJ, Chew SJ, Marzani D, et al. Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes[J]. Invest Ophthalmol Vis Sci, 1998, 39(12): 2217-2231.
28. Barathi VA, Beuerman RW. Molecular mechanisms of muscarinic receptors in mouse scleral fibroblasts: prior to and after induction of experimental myopia with atropine treatment[J/OL]. Mol Vis, 2011, 17: 680-692[2011-03-09]. https://pubmed.ncbi.nlm.nih.gov/21403852/.
29. Lin HJ, Wan L, Chen WC, et al. Muscarinic acetylcholine receptor 3 is dominant in myopia progression[J]. Invest Ophthalmol Vis Sci, 2012, 53(10): 6519-6525. DOI: 10.1167/iovs.11-9031.
30. Stone RA, Lin T, Laties AM. Muscarinic antagonist effects on experimental chick myopia[J]. Exp Eye Res, 1991, 52(6): 755-758. DOI: 10.1016/0014-4835(91)90027-c.
31. Cottriall CL, McBrien NA. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew[J]. Invest Ophthalmol Vis Sci, 1996, 37(7): 1368-1379.
32. Cottriall CL, Truong HT, McBrien NA. Inhibition of myopia development in chicks using himbacine: a role for M(4) receptors?[J]. Neuroreport, 2001, 12(11): 2453-2456. DOI: 10.1097/00001756-200108080-00033.
33. McBrien NA, Arumugam B, Gentle A, et al. The M4 muscarinic antagonist MT-3 inhibits myopia in chick: evidence for site of action[J]. Ophthalmic Physiol Opt, 2011, 31(5): 529-539. DOI: 10.1111/j.1475-1313.2011.00841.x.
34. McBrien NA, Stell WK, Carr B. How does atropine exert its anti-myopia effects?[J]. Ophthalmic Physiol Opt, 2013, 33(3): 373-378. DOI: 10.1111/opo.12052.
35. Arumugam B, McBrien NA. Muscarinic antagonist control of myopia: evidence for M4 and M1 receptor-based pathways in the inhibition of experimentally-induced axial myopia in the tree shrew[J]. Invest Ophthalmol Vis Sci, 2012, 53(9): 5827-5837. DOI: 10.1167/iovs.12-9943.
36. Nickla DL, Zhu X, Wallman J. Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning[J]. Ophthalmic Physiol Opt, 2013, 33(3): 245-256. DOI: 10.1111/opo.12054.
37. 张立华, 闫东升, 周翔天, 等. 毒蕈碱1型受体在人视网膜色素上皮细胞表达的研究[J]. 中华眼科杂志, 2006, 42(12): 1109-1112. DOI: 10.3760/j:issn:0412-4081.2006.12.011.Zhang LH, Yan DS, Zhou XT, et al. Expression of muscarinic acetylcholine receptor-1 in human retinal pigment epithelium[J]. Chin J Ophthalmol, 2006, 42(12): 1109-1112. DOI: 10.3760/j:issn:0412-4081.2006.12.011.
38. Beach KM, Hung LF, Arumugam B, et al. Adenosine receptor distribution in rhesus monkey ocular tissue[J]. Exp Eye Res, 2018, 174: 40-50. DOI: 10.1016/j.exer.2018.05.020.
39. Cui D, Trier K, Zeng J, et al. Adenosine receptor protein changes in guinea pigs with form deprivation myopia[J]. Acta Ophthalmol, 2010, 88(7): 759-765. DOI: 10.1111/j.1755-3768.2009.01559.x.
40. Cui D, Trier K, Zeng J, et al. Effects of 7-methylxanthine on the sclera in form deprivation myopia in guinea pigs[J]. Acta Ophthalmol, 2011, 89(4): 328-334. DOI: 10.1111/j.1755-3768.2009.01688.x.
41. Walline JJ, Lindsley KB, Vedula SS, et al. Interventions to slow progression of myopia in children[J/OL]. Cochrane Database Syst Rev, 2020, 1(1): CD004916[2020-01-13]. https://pubmed.ncbi.nlm.nih.gov/31930781/. DOI: 10.1002/14651858.CD004916.pub4.
42. Smith EL 3rd, Hung LF, She Z, et al. Topically instilled caffeine selectively alters emmetropizing responses in infant rhesus monkeys[J/OL]. Exp Eye Res, 2021, 203: 108438[2021/01/09]. https://pubmed.ncbi.nlm.nih.gov/33428866/. DOI: 10.1016/j.exer.2021.108438.
43. Liu H, Schaeffel F, Trier K, et al. Effects of 7-methylxanthine on deprivation myopia and retinal dopamine release in chickens[J]. Ophthalmic Res, 2020, 63(3): 347-357. DOI: 10.1159/000502529.

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The role of retinal signaling molecules in the occurrence and progression of myopia

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