The Effect of Wharton Jelly-derived Mesenchymal Stem Cells and Stem Cell Exosomes on Visual Functions in Patients With Retinitis Pigmentosa

Retinitis pigmentosa (RP) is one of the leading causes of vision loss and irreversible blindness. It is stated that 1.4 million people are affected in the world and its prevalence is 1:4000. Stem cell applications are methods that are increasingly gaining importance in the field of regenerative medicine and ophthalmology. In addition to many experimental studies in retinal diseases including retinitis pigmentosa, there are also clinical studies reporting successful results on humans. The most widely used stem-cell group in current clinical practice is mesenchymal stem cells. The advantages are that they are relatively easy to obtain and do not induce severe immune responses. Clinical studies in stem cell therapies for the eye suggest that stem cells benefit the surrounding tissue by secreting support such as growth factors, and extracellular vesicles, mostly due to their trophic and paracrine effects. In intraocular applications, there has been a tendency to apply mesenchymal stem cells around/outside the eye, including subtenon and suprachoroidal application due to side effects such as retinal detachment and epiretinal membrane.

Other cellular products that have been studied in animal studies and clinical research in recent years are exosomes. Exosomes are a subgroup of extracellular vesicles released from cells. Exosomes are extracellular vesicles 30-150 nm in size and carry at least one of the exosomal proteins CD63, CD9, CD81, syntenin-1 and TSG101. Exosomes are secreted from different cells in the organism and are also found in body fluids. Exosomes play a role in the transportation of biomolecules such as lipids, carbohydrates, nucleic acids and proteins from one cell to another and in this way, they function in genetic information transfer, and reprogramming of the opposite cell and intercellular communication. One of the sources of exosomes is mesenchymal stem cells that secrete high amount of exosomes. Mesenchymal stem cell-derived exosomes have been reported to have therapeutic effects, just like mesenchymal stem cells. It is thought that stem cells also exert their clinical effects through paracrine factors they secrete rather than being implanted in the tissue. However, the mechanism of action of mesenchymal stem cells has not been fully understood, and exosomes are thought to contribute to the effect. The storage and durability of exosomes may provide advantages in therapeutic applications compared to mesenchymal stem cells and may provide more immunological advantages in allogeneic applications compared to cellular treatments since they do not contain cells.

One of the sources from which mesenchymal stem cells can be obtained is Wharton jelly, which is the mesenchymal tissue of the umbilical cord. Stem cells originating from Wharton gel are a good source of stem cells due to their high differentiation capacity, high regeneration capacity, constant doubling time, high proliferation capacity, low immunogenicity, and no ethical problems due to non-invasive methods, and easy availability.

This clinical trial will enroll patients diagnosed with retinitis pigmentosa. The diagnosis of RP is made by clinical fundus examination, examinations in our clinic, and genetic analysis.

At the beginning of the study, all volunteers will undergo a full ophthalmologic examination including best-corrected visual acuity, anterior segment and fundus examination with a slit lamp, OCT (optical coherence tomography), VF (visual field), ERG (electroretinogram), mfERG (multifocal ERG), OCTA (optical coherence tomography). Retinal and choroidal thickness and ellipsoid bandwidth in OCT, MD (mean deviation) value showing sensitivity in VF, amplitude and latency times in ERG and mf-ERG, vascular density and vascular flow ratios in OCTA will be recorded.