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MedNext Journal of Medical and Health Sciences
Review
DOI: 10.54448/mdnt22311
Submitted: 08-28-2022
Published: 08-28-2022

Major clinical findings of cellular therapy for intravitreal use in ischemic retinopathy and macular degeneration: a systematic review

Unioftal - Ophthalmology And Eye Plastic, Sao Jose do Rio Preto, Sao Paulo, Brazil
Unioftal - Ophthalmology And Eye Plastic, Sao Jose do Rio Preto, Sao Paulo, Brazil
Unioftal - Ophthalmology And Eye Plastic, Sao Jose do Rio Preto, Sao Paulo, Brazil
Unioftal - Ophthalmology And Eye Plastic, Sao Jose do Rio Preto, Sao Paulo, Brazil
Unioftal - Ophthalmology And Eye Plastic, Sao Jose do Rio Preto, Sao Paulo, Brazil
Unioftal - Ophthalmology And Eye Plastic, Sao Jose do Rio Preto, Sao Paulo, Brazil
FACERES - Faculty of Medicine of Sao Jose do Rio Preto, Sao Paulo, Brazil
Eye diseases Ischemic retinopathies Age-related macular degeneration Cellular therapy Bone Marrow stem cell

Abstract

Introduction: In the scenario of eye diseases, diabetic retinopathy and retinal vein occlusion are the two most common ischemic retinopathies in the world. Ischemia is caused by retinal vascular diseases due to decreased blood perfusion and the appearance of areas of retinal non-perfusion. Also, age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in people over 65 years of age in industrialized countries. By 2020, around 200 million people will be affected by AMD worldwide. Objective: the present systematic review study aimed to highlight the main clinical findings of the treatment of ischemic retinopathy and age-related macular degeneration through cell therapy with bone marrow stem cells. Methods: The rules of the Systematic Review-PRISMA Platform were followed. The search was carried out from March 2022 to June 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: It was found 235 articles involving retinitis pigmentosa, macular degeneration, and bone marrow stem cell therapy. A total of 51 were fully evaluated and 28 studies were included and developed in a systematic review in the results field. The symmetrical Funnel Plot does not suggest a risk of bias between the small sample size studies. It was concluded that intravitreal injection of bone marrow-derived stem cells in a patient with retinal vascular occlusion sequelae demonstrated that the procedure is feasible and safe to be performed in humans as there were no signs of infection, inflammation, or development of intraocular tumor formation. Also, neurotrophic effects correlate with vasculature preservation, suggesting that bone marrow-derived stem cells can be used in the treatment of diseases such as retinal degenerations and vasculopathy that currently lack effective treatment. The authors concluded that stem cells can protect retinal cells from degeneration and also suggested that they were able to replace some types of lost retinal neurons.

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References

  1. Stahl A. The Diagnosis and Treatment of Age-Related Macular Degeneration. Dtsch Arztebl Int. 2020 Jul 20;117(29-30):513-520. doi: 10.3238/arztebl.2020.0513. PMID: 33087239; PMCID: PMC7588619.
  2. Thomas CJ, Mirza RG, Gill MK. Age-Related Macular Degeneration. Med Clin North Am. 2021 May;105(3):473-491. doi: 10.1016/j.mcna.2021.01.003. Epub 2021 Apr 2. PMID: 33926642.
  3. Chakravarthy U, Peto T. Current Perspective on Age-Related Macular Degeneration. JAMA. 2020 Aug 25;324(8):794-795. doi: 10.1001/jama.2020.5576. PMID: 32780786.
  4. Nashine S. Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD). Cells. 2021 Sep 19;10(9):2483. doi: 10.3390/cells10092483. PMID: 34572131; PMCID: PMC8464988.
  5. Zhu ZY, Meng YA, Yan B, Luo J. Effect of anti-VEGF treatment on nonperfusion areas in ischemic retinopathy. Int J Ophthalmol. 2021 Nov 18;14(11):1647-1652. doi: 10.18240/ijo.2021.11.01. PMID: 34804852; PMCID: PMC8569571.
  6. Chen DY, Sun NH, Chen X, Gong JJ, Yuan ST, Hu ZZ, Lu NN, Körbelin J, Fukunaga K, Liu QH, Lu YM, Han F. Endothelium-derived semaphorin 3G attenuates ischemic retinopathy by coordinating β-catenin-dependent vascular remodeling. J Clin Invest. 2021 Feb 15;131(4):e135296. doi: 10.1172/JCI135296. PMID: 33586674; PMCID: PMC7880421.
  7. Heckenlively JR, editor. 1988. Retinitis pigmentosa. J.B. Lippincott Co. Philadelphia, Pennsylvania, USA.
  8. Humphries P, Kenna P, and Farrar GJ. On the molecular genetics of retinitis pigmentosa. Science. 1992, 256:804-808.
  9. Farrar GJ, Kenna PF, Humphries P. On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention. EMBO J. 2002, 21:857-864
  10. Dryja TP. et al. 1990. A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature. 343:364-366.
  11. Bowes C. et al. 1990. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature. 347:677- 680.
  12. Kajiwara K. et al. 1991. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa. Nature. 354:480-483.
  13. Gu, SM. et al. 1997. Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat. Genet. 17:194-197.
  14. Ali, R.R. et al. 2000. Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy. Nat. Gnet. 25:306-310.
  15. Takahashi, M., Miyoshi, H., Verma, I.M., and Gage, F.H. 1999. Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J. Virol. 73:7812-7816.
  16. Acland GM. et al. 2001. Gene therapy restores vision in a canine model of childhood blindness. Nat. Genet. 28:92-95.
  17. Frasson M. et al. 1999. Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse. Nat. Med. 5:1183-1187.
  18. Frasson M. et al. 1999. Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. Invest. Ophthalmol. Vis. Sci. 40:2724-2734.
  19. Berson EL. et al. 1993. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch. Ophthalmol. 111:761-772.
  20. Mohand-Said S. et al. 1998. Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse. Proc. Natl. Acad. Sci. U. S. A. 95:8357-8362.
  21. Asahara T. et al. 1997. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 275:964-967.
  22. Kalka, C. et al. 2000. Vascular endothelial growth factor (165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ. Res. 86:1198-1202.
  23. Gill, M. et al. 2001. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ. Res. 88:167-174.
  24. Kocher, A.A. et al. 2001. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med. 7:430-436.
  25. Grant MB. et al. 2002. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat. Med. 8:607-612.
  26. Macular Photocoagulation Study Group. Recurrent choroidal neovascularization after argon laser photocoagulation for neovascular maculopathy. Arch Ophthalmol 1986;104:503-12.
  27. Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. [Comment on: Arch Ophthalmol 1994 112:874- 5].
  28. Treatment of Age-related Macular Degeneration with Photodynamic Therapy Study Group.Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfirin.Arch Ophthalmol.1999;117:1329-1345.
  29. Verterporfin in Photodynamic Therapy Study Group.Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verterporfin 2-year results of randomized clinical trial incluing lesions with occult but no classic neovascularization-VIP report.Am J Ophthalmol 2001:131:542-560.
  30. Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. 2006 Sep;19(3):361-72.
  31. Landa G, Amde W, Doshi V, Ali A, McGevna L, Gentile RC, Muldoon TO, Walsh JB, Rosen RB. Comparative Study of Intravitreal Bevacizumab (Avastin) versus Ranibizumab (Lucentis) in the Treatment of Neovascular Age-Related Macular Degeneration. Ophthalmologica. 2009 Jul 8;223(6):370- 375.
  32. Mitchell P, Korobelnik JF, Lanzetta P, Holz FG, Pruente C, Schmidt- Erfurth UM, Tano Y, Wolf S. Ranibizumab (Lucentis) in neovascular agerelated macular degeneration: evidence from clinical trials. Br J Ophthalmol. 2009 May 20.
  33. Rudkin AK, Lee AW, Chen CS. Central retinal artery occlusion: timing and mode of presentation. Eur J Neurol. 2009 Jun;16(6):674-7. Epub 2009 Apr 3.
  34. Augsburger JJ, Magargal LE: Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980 Dec; 64(12): 913-7.
  35. Brown G: Retinal arterial occlusive disease. In: Guyer DR, ed. Retina-Vitreous-Macula. Vol. 1. WB Saunders; 1999: 271-85.
  36. Chang PC, Chen WS, Lin HY, Lee HM, Chen SJ. Combined central retinal artery and vein occlusion in a patient with systemic lupus erythematosus and anti-phospholipid syndrome. Lupus. 2010 Feb;19(2):206-9. Epub 2009 Oct 30.
  37. Nagy V, Takacs L, Steiber Z, Pfliegler G, Berta A. Thrombophilic screening in retinal artery occlusion patients. Clin Ophthalmol. 2008 Sep;2(3):557-61.
  38. Brown GC: Retinal artery obstructive disease. In: Ryan SJ, ed. Retina. Vol 2. Mosby-Year Book; 1994:1361-77.
  39. Jonas JB, Witzens-Harig M, Arseniev L, Ho AD. Intravitreal autologous bone marrow-derived mononuclear cell transplantation: a feasibility report. Acta Ophthalmol Scand. 2007 Sep 26.
  40. Aiello LP, Brucker AJ, Chang S, et al. Evolving guidelines for intravitreous injections. Retina 2004:S3-S19.
  41. Siqueira RC, Voltarelli JC, Messias AM, Jorge R. Possible mechanisms of retinal function recovery with the use of cell therapy with bone marrow-derived stem cells. Arquivos brasileiros de oftalmologia. Sep-Oct 2010;73(5):474-479.
  42. Siqueira RC, Messias A, Voltarelli JC, Scott IU, Jorge R. Intravitreal injection of autologous bone marrow-derived mononuclear cells for hereditary retinal dystrophy: a phase I trial. Retina. Jun 2011;31(6):1207-1214.
  43. Siqueira RC, Messias A, Voltarelli JC, Messias K, Arcieri RS, Jorge R. Resolution of macular oedema associated with retinitis pigmentosa after intravitreal use of autologous BM-derived hematopoietic stem cell transplantation. Bone marrow transplantation. Apr 2013;48(4):612-613.
  44. L.Otani, A. et al. 2002. Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat. Med. 8:1004- 1010.
  45. Otani A, Dorrel MI,Kinder K,Moreno SK,Nusinowitz S, Banin E,. Heckenlively J, Friedlander M Clin. Invest. 2004, 114:765-774.
  46. Chiou SH, Kao CL, Peng CH, Chen SJ, Tarng YW, Ku HH, Chen YC, Shyr YM, Liu RS, Hsu CJ, Yang DM, Hsu WM, Kuo CD, Lee CH.A novel in vitro retinal differentiation model by co-culturing adult human bone marrow stem cells with retinal pigmented epithelium cells. Biochem Biophys Res Commun. 2005 Jan 21;326(3):578-85.
  47. Banin E, Obolensky A, Idelson M, Hemo I, Reinhardtz E, Pikarsky E, Ben- Hur T, Reubinoff B. Retinal Incorporation and Differentiation of Neural Precursors Derived from Human Embryonic Stem Cells. Stem Cells. 2005 Aug 25; [Epub ahead of print]
  48. Meyer JS, Katz ML, Maruniak JA, Kirk MD. Embryonic stem cell-derived neural progenitors incorporate into degenerating retina and enhance survival of host photoreceptors. Stem Cells. 2005 Aug 25; [Epub ahead of print].
  49. Meyer JS, Katz ML, Kirk MD. Stem cells for retinal degenerative disorders. Ann N Y Acad Sci. 2005 May;1049:135-45.
  50. Das AM, Zhao X, Ahmad I. Stem cell therapy for retinal degeneration: retinal neurons from heterologous sources. Semin Ophthalmol. 2005 Jan- Mar;20(1):3-10.
  51. Minamino K, Adachi Y, Yamada H, Higuchi A, Suzuki Y, Iwasaki M, Nakano K, Koike Y, Mukaide H, Kiriyama N, Shigematsu A, Matsumura M, Ikehara SLong-term survival of bone marrow-derived retinal nerve cells in the retina. Neuroreport. 2005 Aug 22;16(12):1255-9.

How to Cite

Daher, I. D., Moura, M. I. P., Murad, A. C. S., Ferrari, R. S., Neiva, E. B., Liedtke, F. S., & Zotarelli Filho, I. J. (2022). Major clinical findings of cellular therapy for intravitreal use in ischemic retinopathy and macular degeneration: a systematic review. MedNEXT Journal of Medical and Health Sciences, 3(3). https://doi.org/10.54448/mdnt22311