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.
The volunteers will be randomized into three. The 1st group will be the placebo group (45
volunteers) and 0.5 cc saline physiological saline will be applied to the subtenon space. 2nd
group of patients (45 volunteers) will undergo a subtenon injection of Wharton gel-derived
mesenchymal stem cell suspension. A suspension containing mesenchymal stem cell exosomes from
Wharton jelly will be applied to the subtenon distance to the 3rd group of patients (45
volunteers). A single eye of each volunteer will be included. Informed consent will be
obtained from the volunteers.
Allogeneic human Wharton gel tissue-derived mesenchymal stem cells and their exosomes will be
obtained from healthy female volunteers, who is over 18 years old, under sterile conditions
after HBV, HCV, HIV virus and "Treponema Pallidum" (VDRL) tests were performed. Cord tissue
obtained from birth will be carried in a sterile transfer solution and will be processed to
obtain stem cells in Erciyes University Genome and Stem Cell GMP (good manufacturing
practices) certified laboratories. Exosomes will be obtained by the ultracentrifugation
method in the same facility.
For injection into the subtenon distance, the conjunctiva and tenon will be opened with a
small incision about 10 mm away from the lower temporal area, then 20 gauge curved subtenon
cannula will be advanced parallel to the sclera and injected into the posterior subtenon
area. All volunteers will be prescribed antibiotics and steroid drops after the surgical
procedure.
Full ophthalmological examination and examinations at the beginning of the study will be
performed and recorded again on the 1st day, 1st month, 2nd month, 3rd month and 6th months
of the anterior segment and fundus examination, OCT (optical coherence tomography), VF
(visual field) ), ERG (electroretinogram), mfERG (multifocal ERG), OCTA (optical coherence
tomography) examinations will be performed.
In addition, a questionnaire evaluating the visual functions subjectively will be
administered at the 1st, 3rd and 6th-month visits. (National Eye Institute Visual Functioning
Questionnaire - 25 / National Eye Institute (USA) Visual Function Questionnaire ). Two masked
investigators will perform analyses.
Post-procedure 1st Day, 1st Month, 2nd Month, 3rd Month and 6th Month data will be compared
among study groups and within groups.