A Review on Mesenchymal Stem Cells for Treatment of Retinal Diseases

Abstract

Mesenchymal Stem Cells (MSCs) have been studied extensively for the treatment of several retinal diseases. The therapeutic potential of MSCs lies in its ability to differentiate into multiple lineages and secretome enriched with immunomodulatory, antiangiogenic and neurotrophic factors. Several studies have reported the role of MSCs in repair and regeneration of the damaged retina where the secreted factors from MSCs prevent retinal degeneration, improve retinal morphology and function. MSCs also donate mitochondria to rescue the function of retinal cells and exosomes secreted by MSCs were found to have anti-apoptotic and anti-inflammatory effects. Based on several promising results obtained from the preclinical studies, several clinical trials were initiated to explore the potential advantages of MSCs for the treatment of retinal diseases. This review summarizes the various properties of MSCs that help to repair and restore the damaged retinal cells and its potential for the treatment of retinal degenerative diseases. Key words Retinal regeneration . cell replacement therapy . exosomes . mitochondrial transfer . anti-inflammatory molecules Abbreviations AMD Age-related macular degeneration ABCA4 ATP-binding cassette, sub-family A (ABC1), member 4 ACE2 Angiotensin converting enzyme 2 ADSCs Adipose tissue derived mesenchymal stem cells AMSCs Amniotic membrane derived mesenchymal stem cells APCs Antigen presenting cells ASCs Adipose tissue derived stromal cells BCL-XL B-cell lymphoma-extra-large-protein BCVA Best corrected visual acuity BDNF Brain derived neurotrophic factor BM Bruch's membrane

Mesenchymal stem cell surgery, rescue, and regeneration in glaucomatous optic neuropathy

“…In accordance with our results, many investigators evaluated the safety and e cacy of the MSCs use for retinal diseases and suggest MSCs-mediated neuroprotection [13,[30][31][32].…”

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“…The neurotrophic factors secreted by BMSCs, bind to their cognate receptors on the recipient cells and enhance the neural cell survival, differentiation, axonal outgrowth, neural cell attachment and inhibit neural cell apoptosis. The signaling pathways activated by the NTFs, such as P13K/AKT, P13K/IAP, PLC/IP3/PKC, MAPK/ERK and JAK/STAT3 have neuroprotective effect on the neuro-retinal cells [4]. The neuroprotective role was demonstrated in an ex vivo study by Cui et al, where co-culturing BMSCs with retinal ganglion cells (RGCs) reduced hydrogen peroxide (H 2 O 2 ) induced injury in RGCs through the expression of neurotrophins, BDNF, CNTF and reduced the expression of proinflammatory factors interleukin 1β (IL1β) and tumor necrosis factor α (TNFα) by RGCs [5].…”

“…Pathological retinal angiogenesis, unlike vasculogenesis and physiological angiogenesis, leads to disorderliness and creates physiologically deficient blood vessels that disrupt the neuronal histology. These newly formed blood vessels intrude into the outer retina and the macular pit, where absence of vascularity is essential for human vision [4]. Many retinal pathological conditions lead to aberrant angiogenesis with progressive loss of vision.…”

“…Some studies also tested the functionality of the differentiated cells in in vitro systems. Autologous MSC transplantation could be a promising strategy for cell replacement therapy in retinal diseases, however; further preclinical studies are required to understand the safety, immunogenicity and function of the transplanted cells in vivo [4].…”

“…RP patient-derived iPSCs corrected for mutations in Pro23His variant of rhodopsin (RHO) gene and homozygous Alu insertion in exon 9 of male germ cell-associated kinase (MAK) gene by CRISAP/Cas9 mediated gene editing was proposed for autologous retinal cell replacement. Correction of RPGR gene by CRISPR/Cas9 gene editing also resulted in repair of defective photoreceptors and ciliopathy in the patient iPSC-derived organoids [4].…”