Updated progress in basic research of cell therapy for age-related macular degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

 Peng Jingying , Zhou Xiyuan

Department of Ophthalmology, Second Affiliated Hospital of Medical University of Chongqing, Chongqing 400061, China;

Corresponding author：

Peng Jingying, Email: pyl-jj@163.com

Keywords：

Macular degeneration/therapy; Tissue therapy; Review

DOI：

10.3760/cma.j.cn511434-20190124-00032

Video：

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Age-related macular degeneration (AMD) is a fundus disease characterized by degeneration of retinal photoreceptor cells, RPE cells and choroidal capillaries. The pathogenesis is not clear and there is no effective treatment. Cell therapies can slow or reverse the vision loss of AMD in animal models, which include implantation of bone marrow mesenchymal stem cells, pluripotent stem cells, RPE cells into the subretinal cavity. Therefore, cell therapy is a promising strategy for the treatment of AMD.

Citation： Peng Jingying, Zhou Xiyuan. Updated progress in basic research of cell therapy for age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2020, 36(8): 661-664. doi: 10.3760/cma.j.cn511434-20190124-00032 Copy

1.	Jones MK, Lu B, Girman S, et al. Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases[J]. Prog Retin Eye Res, 2017, 58(5): 1-27. DOI: 10.1016/j.preteyeres.2017.01.004.
2.	Khan KN, Mahroo OA, Khan RS, et al. Differentiating drusen:drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes[J]. Prog Retin Eye Res, 2016, 53: 70-106. DOI: 10.1016/j.preteyeres.2016.04.008.
3.	Kivinen N. The role of autophagy in age-related maculardegeneration (AMD) - studies into the pathogenesis of AMD[J]. Acta Ophthalmol, 2018, 96(5): 531-532. DOI: 10.1111/aos.13772.
4.	Ban N, Lee TJ, Sene A, et al. Impaired monocyte cholesterol clearance initiates age-related retinal degeneration and vision loss[J/OL]. JCI Insight, 2018, 3(17): 120824[2019-09-06]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171801/. DOI: 10.1172/jci.insight.120824.
5.	Bergen AA, Arya S, Koster C, et al. On the origin of proteins in human drusen: the meet, greet and stick hypothesis[J]. Prog Retin Eye Res, 2019, 70: 55-84. DOI: 10.1016/j.preteyeres.2018.12.003.
6.	Farnoodian M, Sorenson CM, Sheibani N. Negative regulators of angiogenesis, ocular vascular homeostasis, and pathogenesis and treatment of exudative AMD[J]. J Ophthalmic Vis Res, 2018, 13(4): 470-486. DOI: 10.4103/jovr.jovr_67_18.
7.	Nowak JZ. AMD--the retinal disease with an unprecised etiopathogenesis: in search of effective therapeutics[J]. Acta Pol Pharm, 2014, 71(6): 900-916.
8.	van Lookeren Campagne M, LeCouter J, Yaspan BL, et al. Mechanisms of age-related macular degeneration and therapeutic opportunities[J]. J Pathol, 2014, 232(2): 151-164. DOI: 10.1002/path.4266.
9.	Golestaneh N, Chu Y, Xiao YY, et al. Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration[J/OL]. Cell Death Dis, 2017, 8(1): 2537[2017-01-05]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386365/. DOI: 10.1038/cddis.2016.453.
10.	Mitchell P, Liew G, Gopinath B, et al. Age-related macular degeneration[J]. Lancet, 2018, 392(10153): 1147-1159. DOI: 10.1016/S0140-6736(18)31550-2.
11.	Cislo-Pakuluk A, Marycz K. A promising tool in retina regeneration: current perspectives and challenges when using mesenchymal progenitor stem cells in veterinary and human ophthalmological applications[J]. Stem Cell Rev, 2017, 13(5): 598-602. DOI: 10.1007/s12015-017-9750-4.
12.	Decembrini S, Martin C, Sennlaub F, et al. Cone genesis tracing by the Chrnb4-EGFP mouse line: evidences of cellular material fusion after cone precursor transplantation[J]. Mol Ther, 2017, 25(3): 634-653. DOI: 10.1016/j.ymthe.2016.12.015.
13.	Canto-Soler V, Flores-Bellver M, Vergara MN. Stem cell sources and their potential for the treatment of retinal degenerations[J]. Invest Ophthalmol Vis Sci, 2016, 57(5): 1-9. DOI: 10.1167/iovs.16-19127.
14.	Kirchhof B. Cell transplantation in age-related macular degeneration[J]. Klin Monbl Augenheilkd, 2017, 234(9): 1082-1087. DOI: 10.1055/s-0043-111802.
15.	Bracha P, Moore NA, Ciulla TA. Induced pluripotent stem cell-based therapy for age-related macular degeneration[J]. Expert Opin Biol Ther, 2017, 17(9): 1113-1126. DOI: 10.1080/14712598.2017.1346079.
16.	Bennis A, Jacobs JG, Catsburg LAE, et al. Stem cell derived retinal pigment epithelium: the role of pigmentation as maturation marker and gene expression profile comparison with human endogenous retinal pigment epithelium[J]. Stem Cell Rev, 2017, 13(5): 659-669. DOI: 10.1007/s12015-017-9754-0.
17.	Bennis A, Ten Brink JB, Moerland PD, et al. Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium[J/OL]. PLoS One, 2017, 12(8): 0182983[2017-08-21]. https://doi.org/10.1371/journal.pone.0182983. DOI: 10.1371/journal.pone.0182983.
18.	Kharitonov AE, Surdina AV, Lebedeva OS, et al. Possibilities for using pluripotent stem cells for restoring damaged eye retinal pigment epithelium[J]. Acta Naturae, 2018, 10(3): 30-39. DOI: 10.32607/20758251-2018-10-3-30-39.
19.	Sugita S, Iwasaki Y, Makabe K, et al. Successful transplantation of retinal pigment epithelial cells from MHC homozygote iPSCs in MHC-matched models[J]. Stem Cell Reports, 2016, 7(4): 635-648. DOI: 10.1016/j.stemcr.2016.08.010.
20.	Borsch O, Santos-Ferreira T, Ader M. Photoreceptor transplantation into the degenerative retina[J]. Klin Monbl Augenheilkd, 2017, 234(3): 343-353. DOI: 10.1055/s-0043-104421.
21.	Hu Q, Chen R, Teesalu T, et al. Reprogramming human retinal pigmented epithelial cells to neurons using recombinant proteins[J]. Stem Cells Transl Med, 2014, 3(12): 1526-1534. DOI: 10.5966/sctm.2014-0038.
22.	Moreno AM, Fu X, Zhu J, et al. In situ gene therapy via AAV-CRISPR-Cas9-mediated targeted gene regulation[J]. Mol Ther, 2018, 26(7): 1818-1827. DOI: 10.1016/j.ymthe.2018.04.017.
23.	Hunt NC, Hallam D, Karimi A, et al. 3D culture of human pluripotent stem cells in RGD-alginate hydrogel improves retinal tissue development[J]. Acta Biomater, 2017, 49(2): 329-343. DOI: 10.1016/j.actbio.2016.11.016.
24.	Lipecz A, Miller L, Kovacs I, et al. Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions[J]. Geroscience, 2019, 41(6): 813-845. DOI: 10.1007/s11357-019-00138-3.
25.	Gagliardi G, Ben M'Barek K, Chaffiol A, et al. Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids[J]. Stem Cell Reports, 2018, 11(3): 665-680. DOI: 10.1016/j.stemcr.2018.07.005.
26.	Amram B, Cohen-Tayar Y, David A, et al. The retinal pigmented epithelium - from basic developmental biology research to translational approaches[J]. Int J Dev Biol, 2017, 61(3-4-5): 225-234. DOI: 10.1387/ijdb.160393ra.
27.	Forest DL, Johnson LV, Clegg DO. Cellular models and therapies for age-related macular degeneration[J]. Dis Model Mech, 2015, 8(5): 421-427. DOI: 10.1242/dmm.017236.
28.	Nishiguchi KM, Fujita K, Tokashiki N, et al. Retained plasticity and substantial recovery of rod-mediated visual acuity at the visual cortex in blind adult mice with retinal dystrophy[J]. Mol Ther, 2018, 26(10): 2397-2406. DOI: 10.1016/j.ymthe.2018.07.012.
29.	Yanagi Y, Foo VHX, Yoshida A. Asian age-related macular degeneration: from basic science research perspective[J]. Eye(Lond), 2019, 33(1): 34-49. DOI: 10.1038/s41433-018-0225-x.
30.	Holan V, Hermankova B, Kossl J. Perspectives of stem cell-based therapy for age-related retinal degenerative diseases[J]. Cell Transplant, 2017, 26(9): 1538-1541. DOI: 10.1177/0963689717721227.
31.	Slembrouck-Brec A, Rodrigues A, Rabesandratana O, et al. Reprogramming of adult retinal Müller glial cells into human-induced pluripotent stem cells as an efficient source of retinal cells [J/OL]. Stem Cells Int, 2019, 2019: 7858796[2019-07-15]. https://doi.org/10.1155/2019/7858796. DOI: 10.1155/2019/7858796.
32.	Gasparini SJ, Llonch S, Borsch O, et al. Transplantation of photoreceptors into the degenerative retina:current state and future perspectives[J]. Prog Retin Eye Res, 2019, 69: 1-37. DOI: 10.1016/j.preteyeres.2018.11.001.
33.	Puertas-Neyra K, Usategui-Martín R, Coco RM, et al. Intravitreal stem cell paracrine properties as a potential neuroprotective therapy for retinal photoreceptor neurodegenerative diseases[J]. Neural Regen Res, 2020, 15(9): 1631-1638. DOI: 10.4103/1673-5374.276324.
34.	Kuroda T, Ando S, Takeno Y, et al. Robust induction of retinal pigment epithelium cells from human induced pluripotent stem cells by inhibiting FGF/MAPK signaling[J/OL]. Stem Cell Res, 2019, 39: 101514[2019-08-01]. https://doi.org/10.1016/j.scr.2019.101514. DOI: 10.1016/j.scr.2019.101514.
35.	Léveillard T, Philp NJ, Sennlaub F. Is retinal metabolic dysfunction at the center of the pathogenesis of age-related macular degeneration?[J]. Int J Mol Sci, 2019, 20(3): 762. DOI: 10.3390/ijms20030762.

1. Jones MK, Lu B, Girman S, et al. Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases[J]. Prog Retin Eye Res, 2017, 58(5): 1-27. DOI: 10.1016/j.preteyeres.2017.01.004.
2. Khan KN, Mahroo OA, Khan RS, et al. Differentiating drusen:drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes[J]. Prog Retin Eye Res, 2016, 53: 70-106. DOI: 10.1016/j.preteyeres.2016.04.008.
3. Kivinen N. The role of autophagy in age-related maculardegeneration (AMD) - studies into the pathogenesis of AMD[J]. Acta Ophthalmol, 2018, 96(5): 531-532. DOI: 10.1111/aos.13772.
4. Ban N, Lee TJ, Sene A, et al. Impaired monocyte cholesterol clearance initiates age-related retinal degeneration and vision loss[J/OL]. JCI Insight, 2018, 3(17): 120824[2019-09-06]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171801/. DOI: 10.1172/jci.insight.120824.
5. Bergen AA, Arya S, Koster C, et al. On the origin of proteins in human drusen: the meet, greet and stick hypothesis[J]. Prog Retin Eye Res, 2019, 70: 55-84. DOI: 10.1016/j.preteyeres.2018.12.003.
6. Farnoodian M, Sorenson CM, Sheibani N. Negative regulators of angiogenesis, ocular vascular homeostasis, and pathogenesis and treatment of exudative AMD[J]. J Ophthalmic Vis Res, 2018, 13(4): 470-486. DOI: 10.4103/jovr.jovr_67_18.
7. Nowak JZ. AMD--the retinal disease with an unprecised etiopathogenesis: in search of effective therapeutics[J]. Acta Pol Pharm, 2014, 71(6): 900-916.
8. van Lookeren Campagne M, LeCouter J, Yaspan BL, et al. Mechanisms of age-related macular degeneration and therapeutic opportunities[J]. J Pathol, 2014, 232(2): 151-164. DOI: 10.1002/path.4266.
9. Golestaneh N, Chu Y, Xiao YY, et al. Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration[J/OL]. Cell Death Dis, 2017, 8(1): 2537[2017-01-05]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386365/. DOI: 10.1038/cddis.2016.453.
10. Mitchell P, Liew G, Gopinath B, et al. Age-related macular degeneration[J]. Lancet, 2018, 392(10153): 1147-1159. DOI: 10.1016/S0140-6736(18)31550-2.
11. Cislo-Pakuluk A, Marycz K. A promising tool in retina regeneration: current perspectives and challenges when using mesenchymal progenitor stem cells in veterinary and human ophthalmological applications[J]. Stem Cell Rev, 2017, 13(5): 598-602. DOI: 10.1007/s12015-017-9750-4.
12. Decembrini S, Martin C, Sennlaub F, et al. Cone genesis tracing by the Chrnb4-EGFP mouse line: evidences of cellular material fusion after cone precursor transplantation[J]. Mol Ther, 2017, 25(3): 634-653. DOI: 10.1016/j.ymthe.2016.12.015.
13. Canto-Soler V, Flores-Bellver M, Vergara MN. Stem cell sources and their potential for the treatment of retinal degenerations[J]. Invest Ophthalmol Vis Sci, 2016, 57(5): 1-9. DOI: 10.1167/iovs.16-19127.
14. Kirchhof B. Cell transplantation in age-related macular degeneration[J]. Klin Monbl Augenheilkd, 2017, 234(9): 1082-1087. DOI: 10.1055/s-0043-111802.
15. Bracha P, Moore NA, Ciulla TA. Induced pluripotent stem cell-based therapy for age-related macular degeneration[J]. Expert Opin Biol Ther, 2017, 17(9): 1113-1126. DOI: 10.1080/14712598.2017.1346079.
16. Bennis A, Jacobs JG, Catsburg LAE, et al. Stem cell derived retinal pigment epithelium: the role of pigmentation as maturation marker and gene expression profile comparison with human endogenous retinal pigment epithelium[J]. Stem Cell Rev, 2017, 13(5): 659-669. DOI: 10.1007/s12015-017-9754-0.
17. Bennis A, Ten Brink JB, Moerland PD, et al. Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium[J/OL]. PLoS One, 2017, 12(8): 0182983[2017-08-21]. https://doi.org/10.1371/journal.pone.0182983. DOI: 10.1371/journal.pone.0182983.
18. Kharitonov AE, Surdina AV, Lebedeva OS, et al. Possibilities for using pluripotent stem cells for restoring damaged eye retinal pigment epithelium[J]. Acta Naturae, 2018, 10(3): 30-39. DOI: 10.32607/20758251-2018-10-3-30-39.
19. Sugita S, Iwasaki Y, Makabe K, et al. Successful transplantation of retinal pigment epithelial cells from MHC homozygote iPSCs in MHC-matched models[J]. Stem Cell Reports, 2016, 7(4): 635-648. DOI: 10.1016/j.stemcr.2016.08.010.
20. Borsch O, Santos-Ferreira T, Ader M. Photoreceptor transplantation into the degenerative retina[J]. Klin Monbl Augenheilkd, 2017, 234(3): 343-353. DOI: 10.1055/s-0043-104421.
21. Hu Q, Chen R, Teesalu T, et al. Reprogramming human retinal pigmented epithelial cells to neurons using recombinant proteins[J]. Stem Cells Transl Med, 2014, 3(12): 1526-1534. DOI: 10.5966/sctm.2014-0038.
22. Moreno AM, Fu X, Zhu J, et al. In situ gene therapy via AAV-CRISPR-Cas9-mediated targeted gene regulation[J]. Mol Ther, 2018, 26(7): 1818-1827. DOI: 10.1016/j.ymthe.2018.04.017.
23. Hunt NC, Hallam D, Karimi A, et al. 3D culture of human pluripotent stem cells in RGD-alginate hydrogel improves retinal tissue development[J]. Acta Biomater, 2017, 49(2): 329-343. DOI: 10.1016/j.actbio.2016.11.016.
24. Lipecz A, Miller L, Kovacs I, et al. Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions[J]. Geroscience, 2019, 41(6): 813-845. DOI: 10.1007/s11357-019-00138-3.
25. Gagliardi G, Ben M'Barek K, Chaffiol A, et al. Characterization and transplantation of CD73-positive photoreceptors isolated from human iPSC-derived retinal organoids[J]. Stem Cell Reports, 2018, 11(3): 665-680. DOI: 10.1016/j.stemcr.2018.07.005.
26. Amram B, Cohen-Tayar Y, David A, et al. The retinal pigmented epithelium - from basic developmental biology research to translational approaches[J]. Int J Dev Biol, 2017, 61(3-4-5): 225-234. DOI: 10.1387/ijdb.160393ra.
27. Forest DL, Johnson LV, Clegg DO. Cellular models and therapies for age-related macular degeneration[J]. Dis Model Mech, 2015, 8(5): 421-427. DOI: 10.1242/dmm.017236.
28. Nishiguchi KM, Fujita K, Tokashiki N, et al. Retained plasticity and substantial recovery of rod-mediated visual acuity at the visual cortex in blind adult mice with retinal dystrophy[J]. Mol Ther, 2018, 26(10): 2397-2406. DOI: 10.1016/j.ymthe.2018.07.012.
29. Yanagi Y, Foo VHX, Yoshida A. Asian age-related macular degeneration: from basic science research perspective[J]. Eye(Lond), 2019, 33(1): 34-49. DOI: 10.1038/s41433-018-0225-x.
30. Holan V, Hermankova B, Kossl J. Perspectives of stem cell-based therapy for age-related retinal degenerative diseases[J]. Cell Transplant, 2017, 26(9): 1538-1541. DOI: 10.1177/0963689717721227.
31. Slembrouck-Brec A, Rodrigues A, Rabesandratana O, et al. Reprogramming of adult retinal Müller glial cells into human-induced pluripotent stem cells as an efficient source of retinal cells [J/OL]. Stem Cells Int, 2019, 2019: 7858796[2019-07-15]. https://doi.org/10.1155/2019/7858796. DOI: 10.1155/2019/7858796.
32. Gasparini SJ, Llonch S, Borsch O, et al. Transplantation of photoreceptors into the degenerative retina:current state and future perspectives[J]. Prog Retin Eye Res, 2019, 69: 1-37. DOI: 10.1016/j.preteyeres.2018.11.001.
33. Puertas-Neyra K, Usategui-Martín R, Coco RM, et al. Intravitreal stem cell paracrine properties as a potential neuroprotective therapy for retinal photoreceptor neurodegenerative diseases[J]. Neural Regen Res, 2020, 15(9): 1631-1638. DOI: 10.4103/1673-5374.276324.
34. Kuroda T, Ando S, Takeno Y, et al. Robust induction of retinal pigment epithelium cells from human induced pluripotent stem cells by inhibiting FGF/MAPK signaling[J/OL]. Stem Cell Res, 2019, 39: 101514[2019-08-01]. https://doi.org/10.1016/j.scr.2019.101514. DOI: 10.1016/j.scr.2019.101514.
35. Léveillard T, Philp NJ, Sennlaub F. Is retinal metabolic dysfunction at the center of the pathogenesis of age-related macular degeneration?[J]. Int J Mol Sci, 2019, 20(3): 762. DOI: 10.3390/ijms20030762.

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