Recent approaches to ameliorate vision by stem cell therapy

Negar Foroughi,1,* Maede fekri abras,2

Abstract

Introduction

Casting a close glance at the soaring number of people who are suffering from vision impairment in the elderly all around the world, has given us the importance of regenerating traumatized tissues with age-related macular degeneration deploying human embryonic stem cells due to its self-renewal ability. in recent years omnipotent embryonic stem cells have been holding a great promise to treat an array of disorders. they can differentiate into any cell with different features to regenerate a specific tissue giving people with age-related macular degeneration (amd) and stargardt macular dystrophy (stdg1) a vision improvement by engraftment of human embryonic stem cell-derived retinal pigment epithelium into subretinal space.

Methods

This review was written based on recent discoveries in the field of photoreceptor transplantation therapy from 2006 to 2018 of 57 specifically-related articles to amd stem-cell therapy in asian, european and american countries from ncbi, elsevier, and pub med sites. valid data of each article, which was clinically successful in recovering vision to some extent, was selected and brought here in addition to the results of the experiments.

Results

Hescs-derived rpe mao9 were generated and cryopreserved. thawed rpe differentiated colonies were picked up by means of collagenase. in addition, nic (nicotinamide) stimulated the appearance of pigmentation within the differentiating clusters. 99% of hrpe were stained for their expressed markers such as zo1, pa-6, mite, and bestrophin in fluorescence-activated cell sorting (facs) and fluorescein angiography in a heterogeneous fluid mixture, or phagocytized the fluorescently labeled beads in phagocytosis assay kit. preretinal pigmented cell growth was seen in a few eyes near the injection site, but does not exert an adverse influence over their vision nevertheless. a number of selected individuals both with adm degeneration and stdg dystrophy were undergone pars plana vitrectomy, including surgical induction of posterior vitreous separation from the optic nerve, in order to inject rpe while immuno-suppressive drugs have been administered before and after the surgical procedure. in some eyes, small pigmented clumps were observed in the fundus photographs in optical coherence tomography (oct) and resolved within 11-12 months. despite developing visually remarkable progression cataract and the following decrease in visual acuity (va) for a few eyes, eyesight improved after the cataract surgery. some eyes were infected and led to severe inflammation which treated by taking antibiotic drops and discontinuation of immunosuppression. in some cases, a cessation of immunosuppression was done because of repeatedly elevated creatinine levels in serum, blood urea nitrogen (bun) levels, and potassium as well as bone marrow suppression. small patches of pigmented growth lining aspects of bruch membrane, was seen in a few eyes. treated eyes were trialed with electroretinography (erg) measuring the electrical response imaging of rods and cones. after all, most patients va has improved and no diminution of visual has reported except in a few rare cases, though transplanted patients must be assessed by plenty of examinations including; tomography, flow cytometry.

Conclusion

Importance of precarious challenges of stem cell therapy has led to some suggesting ideas to alleviate the possible risks, like; hyperproliferation of the cells which might develop tumors or even retinoblastoma. one of the main concerns is the probability of tissue rejection which immunosuppression drugs administered to reduce the allograft rejection. also, h1 and h9 hescs, which does not cause an immunological response, could be used due to the low expression of the major histoincompatibility complex (mhci) and no expression of mhcii. if we use autologous hescs from saved umbilical cord or adult bone marrow cells, rpe cells will not be recognized by the immune system so that there would be no need for immunosuppressive drugs to weaken the immune system which raises the possibility of infection and inflammation. choroidal neovascularization is associated with rpe atrophy in adm patients that may be a result of defects in bruch membrane during the hrpe injection procedure. in some patients, the cataract may happen in association with retinal dystrophy. after the cataract surgery, their vision will recover completely.

Keywords

Macular degeneration, retinal stem cell therapy, retina regenerative medicine, retinal engraftment.