A Promising Tool in Retina Regeneration: Current Perspectives and Challenges When Using Mesenchymal Progenitor Stem Cells in Veterinary and Human Ophthalmological Applications

Abstract

Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748–760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al. Investigative Opthalmology & Visual Science, 50(9), 4244, 2009; Bull et al. Investigative Opthalmology & Visual Science, 49(8), 3449, 2008; Yu et al. Biochemical and Biophysical Research Communications, 344(4), 1071-1079, 2006; Na et al. Graefe's Archive for Clinical and Experimental Ophthalmology, 247(4), 503-514, 2008). In previous studies, some of the stem cell variants used include human Muller SCs and bone marrow derived SCs. Some of the regenerative potential characteristics of mesenchymal progenitor stem cells (MSCs) include their multilineage differentiation potential, their immunomodulatory effects, their high proliferative activity, they can be easily cultured in vitro, and finally their potential to synthesize and secrete membrane derived vesicles rich in growth factors, mRNA and miRNA which possibly aid in regulation of tissue damage regeneration. These facts alone, explain why MSCs are so widely used in clinical trials, 350 up to date (Switonski, Reproductive Biology, 14(1), 44–50, 2014). Animal studies have demonstrated that sub-retinal transplantation of MSCs delays retinal degeneration and preserves retinal function through trophic response (Inoue et al. Experimental Eye Research, 85(2), 234–241, 2007). Umbilical cord derived MSCs (UC/MSCs) have also been shown to contain neuroprotective features of ganglion cells in rat studies (Zwart et al. Experimental Neurology, 216(2), 439–448, 2009). This review aims to present current MSC therapies in practice, as well as their retinal regeneration potential in animal models, and their innovative prospects for treatment of human retinal diseases.

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

“…WJ-MSCs have been shown to suppress chronic inflammation and prevent apoptosis in animal models of neurodegenerative and ischemic retinal disorders [27,28]. WJ-MSCs also stimulate progenitor cells in the retina and elicit selfrepair mechanisms [29,30].…”

Neuroprotection in glaucoma: recent advances and clinical translation

“…84,[86][87][88] Recently, plateletderived growth factor produced by human MSCs has been shown to have a strong neuroprotective action on human RGCs (undertaken on human donor retinal explants). 84,[86][87][88] Recently, plateletderived growth factor produced by human MSCs has been shown to have a strong neuroprotective action on human RGCs (undertaken on human donor retinal explants).…”

“…82,86,87 Furthermore, there was limited differentiation of MSCs to retinal neuronal cells or RGC with functional axons and this was reflective of poor integration of grafted MSCs into the retinal tissue or optic tract. 88 88 …”

“…The attenuation of RGC death by MSC transplantation is largely attributed to the extended release of trophic factors by the transplanted cells such as CNTF, bFGF, GDNF, Hepatocyte Growth Factor alpha (HGFα) and BDNF. 84,[86][87][88] Recently, plateletderived growth factor produced by human MSCs has been shown to have a strong neuroprotective action on human RGCs (undertaken on human donor retinal explants). 89 CNTF is a potent RGC survival factor and bFGF is a stimulator of axonal growth.…”

“…83,86,87 Therefore, stem cells used as a vector for delivery and secretion of neurotrophic factors to repair damaged RCGs could be more advantageous than their seemingly limited ability to integrate and differentiate to repopulate retinal neuronal tissue in POAG. 88…”