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Mesenchymal stem cells improve healing of the cornea after alkali injury

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Abstract

Purpose

To evaluate the efficacy of mesenchymal stem cells (MSCs) to ameliorate the consequences of corneal alkali injuries.

Methods

Corneal alkali injuries were created in 30 rabbit eyes. The MSC group (n = 15) were treated with intrastromal and subconjunctival injections of phosphate-buffered saline (PBS) containing 2 × 106 MSCs and topical application. The control group (n = 15) was treated with PBS by the same applications forms. Drops of standard treatment (ascorbate 10 %, citrate 10 %, tobramycin, dexamethasone, Cyclogyl) were instilled for 2 weeks. Rabbits underwent slit-lamp examination, fluorescein staining, photography, and were evaluated for corneal neovascularization, opacification, and epithelial defects. Tear secretion and IOP were also evaluated. Furthermore, the concentration of Serumglutamic–pyruvic transaminase (SGPT) and vascular endothelial factor (VEGF) were measured. Immunohistochemistry was also performed for a-SMA and Ki-67.

Results

Eyes treated with MSCs showed better recovery. The mean neovascularized area was significantly smaller in the MSC group (p < 0.05). A significant difference in the degree of corneal opacification and re-epithelialization was also observed, as well as the IOP at 21 and 28 posttraumatic days (p < 0.05). Histology showed that MSCs resulted in almost normal architecture of eye tissues. After the MSCs infusion, SGPT and VEGF levels in cornea were significantly reduced. Immunohistochemistry demonstrated a reduction of a-SMA in the MSC group with higher mitotic-regenerative activity with the presence of Ki67.

Conclusions

Our study represents a first step in understanding the possibilities of the MSC approach to treatment of alkali injuries of the cornea and shows that such an approach improves clinical outcomes and leads to better prognosis.

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Ethical standards

The study was approved by the local Ethics Committee of the Aristotle University of Thessaloniki as well as by the Committee of the Veterinary Medicine of Thessaloniki and have therefore been performed in accordance with the ethical standards of Declaration of Helsinki and its later amendments.

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Authors and Affiliations

  1. Laboratory of Experimental Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Diamantis Almaliotis, Ilias Nakos & Vasileios Karampatakis

  2. Department of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Georgios Koliakos

  3. Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Eleni Papakonstantinou

  4. School of Veterinary Medicine, Faculty of health sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Anastasia Komnenou & Angelos Thomas

  5. Biohellenika Biotechnology Company, 57001, Thessaloniki, Greece

    Georgios Koliakos & Spiros Petrakis

  6. Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Eleni Gounari

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  1. Diamantis Almaliotis
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  2. Georgios Koliakos
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Almaliotis, D., Koliakos, G., Papakonstantinou, E. et al. Mesenchymal stem cells improve healing of the cornea after alkali injury. Graefes Arch Clin Exp Ophthalmol 253, 1121–1135 (2015). https://doi.org/10.1007/s00417-015-3042-y

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