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Vol 81, No 4 (2022)
Original article
Submitted: 2021-06-02
Accepted: 2021-08-23
Published online: 2021-09-10
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The potential therapeutic efficacy of intravenous versus subconjunctival mesenchymal stem cells on experimentally ultraviolet-induced corneal injury in adult male albino rats

W. A. Nasr El-Din12, N. Nooreldin3, A. S. Essawy34
DOI: 10.5603/FM.a2021.0085
·
Pubmed: 34545564
·
Folia Morphol 2022;81(4):900-916.
Affiliations
  1. Department of Anatomy, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
  2. Department of Human Anatomy and Embryology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
  3. Department of Human Anatomy and Embryology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
  4. Anatomy Department, Ibn Sina National College for Medical Studies, Jeddah, KSA

open access

Vol 81, No 4 (2022)
ORIGINAL ARTICLES
Submitted: 2021-06-02
Accepted: 2021-08-23
Published online: 2021-09-10

Abstract

Background: The X-rays and the visible light are the main source of ultraviolet radiation (UVR). About 90% of ultraviolet B (UVB) is absorbed by the cornea which may promote corneal inflammation, oedema and damage of its epithelial layer. Bone marrow mesenchymal stem cells (BM-MSCs) have been demonstrated to ameliorate the injured corneal tissue and accelerate its wound healing. This study aimed to compare the healing effect of intravenous (IV) versus subconjunctival (SC) BM-MSCs on the rats’ corneas subjected to UVB-irradiation.
Materials and methods: Ten rats were used as donors for BM-MSCs and the other 40 were allocated into four equal groups: group I (control group), group II (ultraviolet-irradiated group), group III (ultraviolet-irradiated + IV BM-MSCs-treated group) and group IV (ultraviolet-irradiated +SC BM-MSCs-treated group). Rats of all groups were euthanized after 3 weeks and the corneal specimens were processed for histopathological, immunohistochemical and electron microscopy assessment.
Results: Ultraviolet-irradiated group showed remarkable thinning of epithelial thickness, wide partial epithelial separation, and desquamation. Neovascularisation of the disorganised stroma and disrupted Descemet’s membrane were observed. The superficial and basal epithelial cells appeared irregular and separated by wide intercellular spaces and inflammatory cells. Immunohistochemical examination showed a significant decrease in proliferating cell nuclear antigen immunoreaction. In contrast, minimal changes were observed in rats treated with BM-MSCs with more improvement associated with the subconjunctival administration compared to IV route.
Conclusions: Local SC injection of BM-MSCs has an amazing regenerative efficacy on the corneal injury compared to the systemic IV route.

Abstract

Background: The X-rays and the visible light are the main source of ultraviolet radiation (UVR). About 90% of ultraviolet B (UVB) is absorbed by the cornea which may promote corneal inflammation, oedema and damage of its epithelial layer. Bone marrow mesenchymal stem cells (BM-MSCs) have been demonstrated to ameliorate the injured corneal tissue and accelerate its wound healing. This study aimed to compare the healing effect of intravenous (IV) versus subconjunctival (SC) BM-MSCs on the rats’ corneas subjected to UVB-irradiation.
Materials and methods: Ten rats were used as donors for BM-MSCs and the other 40 were allocated into four equal groups: group I (control group), group II (ultraviolet-irradiated group), group III (ultraviolet-irradiated + IV BM-MSCs-treated group) and group IV (ultraviolet-irradiated +SC BM-MSCs-treated group). Rats of all groups were euthanized after 3 weeks and the corneal specimens were processed for histopathological, immunohistochemical and electron microscopy assessment.
Results: Ultraviolet-irradiated group showed remarkable thinning of epithelial thickness, wide partial epithelial separation, and desquamation. Neovascularisation of the disorganised stroma and disrupted Descemet’s membrane were observed. The superficial and basal epithelial cells appeared irregular and separated by wide intercellular spaces and inflammatory cells. Immunohistochemical examination showed a significant decrease in proliferating cell nuclear antigen immunoreaction. In contrast, minimal changes were observed in rats treated with BM-MSCs with more improvement associated with the subconjunctival administration compared to IV route.
Conclusions: Local SC injection of BM-MSCs has an amazing regenerative efficacy on the corneal injury compared to the systemic IV route.

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Keywords

ultraviolet radiation, corneal injury, mesenchymal stem cells, rats

About this article
Title

The potential therapeutic efficacy of intravenous versus subconjunctival mesenchymal stem cells on experimentally ultraviolet-induced corneal injury in adult male albino rats

Journal

Folia Morphologica

Issue

Vol 81, No 4 (2022)

Article type

Original article

Pages

900-916

Published online

2021-09-10

Page views

4280

Article views/downloads

691

DOI

10.5603/FM.a2021.0085

Pubmed

34545564

Bibliographic record

Folia Morphol 2022;81(4):900-916.

Keywords

ultraviolet radiation
corneal injury
mesenchymal stem cells
rats

Authors

W. A. Nasr El-Din
N. Nooreldin
A. S. Essawy

References (64)
  1. Ahmed SK, Soliman AA, Omar SMM, et al. Bone Marrow Mesenchymal Stem Cell Transplantation in a Rabbit Corneal Alkali Burn Model (A Histological and Immune Histo-chemical Study). Int J Stem Cells. 2015; 8(1): 69–78.
    CrossRefPubMed
  2. Alexander G, Carlsen H, Blomhoff R. Corneal NF-kappaB activity is necessary for the retention of transparency in the cornea of UV-B-exposed transgenic reporter mice. Exp Eye Res. 2006; 82(4): 700–709.
    CrossRefPubMed
  3. Ardan T, Němcová L, Bohuslavová B, et al. Reduced levels of tissue inhibitors of metalloproteinases in UVB-irradiated corneal epithelium. Photochem Photobiol. 2016; 92(5): 720–727.
    CrossRefPubMed
  4. Bancroft JD, Gamble M. Theory and practice of histological techniques, 8th ed. Churchill Livingstone Elsevier, Philadelphia, London 2008: 333–354.
  5. Barbash IM, Chouraqui P, Baron J, et al. Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation. 2003; 108(7): 863–868.
    CrossRefPubMed
  6. Buddi R, Lin B, Atilano SR, et al. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002; 50(3): 341–351.
    CrossRefPubMed
  7. Carvalho AM, Yamada A, Golim MA, et al. Characterization of mesenchymal stem cells derived from equine adipose tissue. Arq Bras Med Vet Zootec. 2013; 65(4): 939–945.
    CrossRef
  8. Cejka C, Kossl J, Hermankova B, et al. The healing of oxidative injuries with trehalose in uvb-irradiated rabbit corneas. Oxid Med Cell Longev. 2019; 2019: 1–10.
    CrossRef
  9. Cejka C, Luyckx J, Cejková J. Central corneal thickness considered an index of corneal hydration of the UVB irradiated rabbit cornea as influenced by UVB absorber. Physiol Res. 2012; 61(3): 299–306.
    CrossRefPubMed
  10. Cejková J, Stípek S, Crkovská J, et al. UV Rays, the prooxidant/antioxidant imbalance in the cornea and oxidative eye damage. Physiol Res. 2004; 53(1): 1–10.
    PubMed
  11. Chang JH, Garg NK, Lunde E, et al. Corneal neovascularization: an anti-VEGF therapy review. Surv Ophthalmol. 2012; 57(5): 415–429.
    CrossRefPubMed
  12. Chen BY, Lin DPC, Wu CY, et al. Dietary zerumbone prevents mouse cornea from UVB-induced photokeratitis through inhibition of NF-κB, iNOS, and TNF-α expression and reduction of MDA accumulation. Mol Vis. 2011; 17: 854–863.
    PubMed
  13. Clements JL, Dana R. Inflammatory corneal neovascularization: etiopathogenesis. Semin Ophthalmol. 2011; 26(4-5): 235–245.
    CrossRefPubMed
  14. Diffey B. Sources and measurement of ultraviolet radiation. Methods. 2002; 28(1): 4–13.
    CrossRefPubMed
  15. Downes JE, Swann PG, Holmes RS. Differential corneal sensitivity to ultraviolet light among inbred strains of mice. Correlation of ultraviolet B sensitivity with aldehyde dehydrogenase deficiency. Cornea. 1994; 13(1): 67–72.
    CrossRefPubMed
  16. Eslani M, Putra I, Shen X, et al. Corneal mesenchymal stromal cells are directly antiangiogenic via PEDF and sFLT-1. Invest Ophthalmol Vis Sci. 2017; 58(12): 5507–5517.
    CrossRefPubMed
  17. Filizay MC, Gokcinar NB, Sahinturk V, et al. Evaluation of retinol palmitate treatment of photokeratitis in rat eyes exposed to ultraviolet B radiation. Beyoglu Eye J. 2019; 4(2): 55–61.
    CrossRefPubMed
  18. Gain P, Jullienne R, He Z, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016; 134(2): 167–173.
    CrossRefPubMed
  19. Ghazaryan E, Zhang Y, He Y, et al. Mesenchymal stem cells in corneal neovascularization: Comparison of different application routes. Mol Med Rep. 2016; 14(4): 3104–3112.
    CrossRefPubMed
  20. Giacomini C, Ferrari G, Bignami F, et al. Alkali burn versus suture-induced corneal neovascularization in C57BL/6 mice: an overview of two common animal models of corneal neovascularization. Exp Eye Res. 2014; 121: 1–4.
    CrossRefPubMed
  21. Girolamo DN, Coroneo MT, Wakefield D. UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERK1/2 MAPK-dependent pathway. Invest Ophthalmol Vis Sci. 2003; 44(11): 4705–4714.
    CrossRefPubMed
  22. Golu A, Gheorghişor I, Bălăşoiu AT, et al. The effect of ultraviolet radiation on the cornea - experimental study. Rom J Morphol Embryol. 2013; 54(4): 1115–1120.
    PubMed
  23. Golu T, Mogoantă L, Streba CT, et al. Pterygium: histological and immunohistochemical aspects. Rom J Morphol Embryol. 2011; 52(1): 153–158.
    PubMed
  24. Hamill MB. Corneal trauma. In: Krachmer JH, Mannis MJ, Holland EJ eds. Cornea. 3rd (ed.). Mosby Elsevier, Saint Louis: 2010: 1176–1178.
  25. Harkin DG, Foyn L, Bray LJ, et al. Concise reviews: can mesenchymal stromal cells differentiate into corneal cells? A systematic review of published data. Stem Cells. 2015; 33(3): 785–791.
    CrossRefPubMed
  26. Holan V, Trosan P, Cejka C, et al. A comparative study of the therapeutic potential of mesenchymal stem cells and limbal epithelial stem cells for ocular surface reconstruction. Stem Cells Transl Med. 2015; 4(9): 1052–1063.
    CrossRefPubMed
  27. Hur S, Lee YS, Yoo H, et al. Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-kappaB nuclear localization. J Dermatol Sci. 2010; 59(3): 163–169.
    CrossRefPubMed
  28. Islam MM, Buznyk O, Reddy JC, et al. Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation. NPJ Regen Med. 2018; 3: 2.
    CrossRefPubMed
  29. Jackson P, Blythe D. Immunohistochemical techniques (chapter 18). In: Suvarna SK, Layton C, Bancroft JD (eds.) Theory and practice of histological techniques. 7th ed. Churchill Livingstone of Elsevier, Philadelphia 2013: 381–426.
  30. Kalleny N, Soliman N. Light and electron microscopic study on the effect of topically applied hyaluronic acid on experimentally induced corneal alkali burn in albino rats. Egypt J Histol. 2011; 34(4): 829–848.
    CrossRef
  31. Kean TJ, Lin P, Caplan AI, et al. MSCs: delivery routes and engraftment, cell-targeting strategies, and immune modulation. Stem Cells Int. 2013; 2013: 732742.
    CrossRefPubMed
  32. Kitaichi N, Shimizu T, Yoshida K, et al. Macrophage migration inhibitory factor ameliorates UV-induced photokeratitis in mice. Exp Eye Res. 2008; 86(6): 929–935.
    CrossRefPubMed
  33. Kolozsvári L, Nogradi A, Hopp B, et al. et al.. UV absorbance of the human cornea in the 240- to 400-nm range. Investig Ophthalmol Vis Sci. 2002; 43(7): 2165–2168.
    PubMed
  34. Lattimore MR. Effects of ultraviolet radiation on the oxygen uptake rate of the rabbit cornea. Optom Vis Sci. 1989; 66(2): 117–122.
    CrossRefPubMed
  35. Lattimore M. Glucose concentration profiles of normal and ultraviolet radiation-exposed rabbit corneas. Exp Eye Res. 1988; 47(5): 699–704.
    CrossRef
  36. Lazarus HM, Koc ON, Devine SM, et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005; 11(5): 389–398.
    CrossRefPubMed
  37. Lee DH, Kim JK, Joo CK. Translocation of nuclear factor-kappaB on corneal epithelial cells induced by ultraviolet B irradiation. Ophthalmic Res. 2005; 37(2): 83–88.
    CrossRefPubMed
  38. Li P, Zhang R, Sun H, et al. PKH26 can transfer to host cells in vitro and vivo. Stem Cells Dev. 2013; 22(2): 340–344.
    CrossRefPubMed
  39. Livezeanu C, Crăiţoiu MM, Mănescu R, et al. Angiogenesis in the pathogenesis of pterygium. Rom J Morphol Embryol. 2011; 52(3): 837–844.
    PubMed
  40. Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015; 49: 17–45.
    CrossRefPubMed
  41. Lohan P, Murphy N, Treacy O, et al. Third-party allogeneic mesenchymal stromal cells prevent rejection in a pre-sensitized high-risk model of corneal transplantation. Front Immunol. 2018; 9: 2666.
    CrossRefPubMed
  42. Ma Y, Xu Y, Xiao Z, et al. Reconstruction of chemically burned rat corneal surface by bone marrow-derived human mesenchymal stem cells. Stem Cells. 2006; 24(2): 315–321.
    CrossRefPubMed
  43. Mahmoud B, Shady A, Meleegy UEl, et al. Effects of ultraviolet B radiation on the cornea of adult male albino rats and the possible role of lornoxicam: a histological, immunohistochemical and morphometrical study. Egypt J Histol. 2010; 33(1): 156–167.
    CrossRef
  44. Mittal SK, Omoto M, Amouzegar A, et al. Restoration of corneal transparency by mesenchymal stem cells. Stem Cell Reports. 2016; 7(4): 583–590.
    CrossRefPubMed
  45. Mureşan S, Filip A, Mureşan A, et al. Histological findings in the Wistar rat cornea following UVB irradiation. Rom J Morphol Embryol. 2013; 54(2): 247–252.
    PubMed
  46. Nombela-Arrieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol. 2011; 12(2): 126–131.
    CrossRefPubMed
  47. Oh JY, Kim MK, Shin MiS, et al. The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells. 2008; 26(4): 1047–1055.
    CrossRefPubMed
  48. Olsen EG, Ringvold A. Human cornea endothelium and ultraviolet radiation. Acta Ophthalmol (Copenh). 1982; 60(1): 54–56.
    CrossRefPubMed
  49. Pauloin T, Dutot M, Joly F, et al. High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells. Mol Vision. 2009; 15: 577–583.
    PubMed
  50. Podskochy A. Protective role of corneal epithelium against ultraviolet radiation damage. Acta Ophthalmol Scand. 2004; 82(6): 714–717.
    CrossRefPubMed
  51. Saghizadeh M, Kramerov AA, Svendsen CN, et al. Concise review: stem cells for corneal wound healing. Stem Cells. 2017; 35(10): 2105–2114.
    CrossRefPubMed
  52. Sharaf Eldin H, Ibrahim M, Elswaidy N. A histological and immunohistochemical study of the effect of platelet- rich plasma on a corneal alkali burn in adult male albino rat. Egypt J Histol. 2019; 0(0): 0–0.
    CrossRef
  53. Shukla S, Mittal SK, Foulsham W, et al. Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury. Ocul Surf. 2019; 17(4): 729–736.
    CrossRefPubMed
  54. Sohni A, Verfaillie CM. Mesenchymal stem cells migration homing and tracking. Stem Cells Int. 2013; 2013: 130763.
    CrossRefPubMed
  55. Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc. 2009; 4(1): 102–106.
    CrossRefPubMed
  56. Strober W. Trypan blue exclusion test of cell viability. Curr Protoc Immunol. 2001; Appendix 3: Appendix 3B.
    CrossRefPubMed
  57. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008; 8(9): 726–736.
    CrossRefPubMed
  58. Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol. 2006; 36(10): 2566–2573.
    CrossRefPubMed
  59. Viiri J, Jauhonen HM, Kauppinen A, et al. Cis-urocanic acid suppresses UV-B-induced interleukin-6 and -8 secretion and cytotoxicity in human corneal and conjunctival epithelial cells in vitro. Mol Vis. 2009; 15: 1799–1805.
    PubMed
  60. Wang Z, Handa JT, Green WR, et al. Advanced glycation end products and receptors in Fuchs' dystrophy corneas undergoing Descemet's stripping with endothelial keratoplasty. Ophthalmology. 2007; 114(8): 1453–1460.
    CrossRefPubMed
  61. Yao L, Li Zr, Su Wr, et al. Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn. PLoS One. 2012; 7(2): e30842.
    CrossRefPubMed
  62. Ye J, Yao K, Kim JC. Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing. Eye (Lond). 2006; 20(4): 482–490.
    CrossRefPubMed
  63. Youn HY, McCanna DJ, Sivak JG, et al. In vitro ultraviolet-induced damage in human corneal, lens, and retinal pigment epithelial cells. Mol Vis. 2011; 17: 237–246.
    PubMed
  64. Zhang M, Mal N, Kiedrowski M, et al. SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J. 2007; 21(12): 3197–3207.
    CrossRefPubMed

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