Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases

Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited effects.Among stem cells of different sources,mesenchymal stem cells(MSCs)offer several advantages,such as the absence of ethical concerns,easy harvesting,low immunogenicity and reduced tumorigenesis risks.Other than a multipotent differentiation ability,MSCs can release extracellular vesicles conveying proteins,mRNA and microRNA.Thanks to these properties,new therapeutic approaches have been designed for the treatment of various pathologies,including ocular diseases.In this review,the use of different MSCs and different administration strategies are described for the treatment of diabetic retinopathy,glaucoma,and retinitis pigmentosa.In a large number of investigations,positive results have been obtained by in vitro experiments and by MSC administration in animal models.Most authors agree that beneficial effects are likely related to MSC paracrine activity.Based on these considerations,many clinical trials have already been carried out.Overall,although some adverse effects have been described,promising outcomes are reported.It can be assumed that in the near future,safer and more effective protocols will be developed for more numerous clinical applications to improve the quality of life of patients affected by eye diseases.

An Association of Vitamins A and E with Hyaluronic and Lactobionic Acids may Prevent Molecular Changes Associated with Keratocyte to Myofibroblast Transition

Inflammatory events in the corneal stroma may activate keratocytes and trigger their transition towards myofibroblasts,which now produce different extracellular matrix(ECM)proteins thus causing corneal opacification.Corneal haze is a frequent side effect after photorefractive keratectomy(PRK)to correct high myopia.Currently,a preventive treatment with mitomycin-c can be used to limit the occurrence of this phenomenon.However,mitomycin-c is a toxic drug,not devoid of side effects,which may occasionally involve the corneal endothelium.Therefore,we have searched for a less risky,natural way,to prevent keratocytes transition.To this purpose,we have used as markers of the phenotype switch the proteins lumican(highly expressed by keratocytes and much less by myofibroblasts)and smooth muscle actin(αSMA)(highly expressed by myofibroblasts and poorly found in keratocytes),beside Fibronectin(Fn),the expression of which is also increased by transforming growth factor-beta(TGFβ)treatment.Treatment of human keratocytes with TGFβwas used to induce the protein shift.Among different possible candidates,we have found that vitamins A and E,hyaluronic and lactobionic acids may prevent,either alone,or much better in association,the shift in the ratio between lumican andαSMA and the increased Fn expression.In conclusion,it could be speculated that topic treatment of the ocular surface with an association of these four compounds could be able to prevent or at least limit the occurrence of post-PRK corneal haze,with the additional advantage of lubrication,hydration and antioxidant defense exerted by these molecules.