**Background**
Retinitis pigmentosa (RP) is a group of inherited retinal degenerations characterized by progressive photoreceptor loss, leading to blindness. Current treatments are limited, and gene therapy is challenged by genetic heterogeneity. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exert paracrine effects by secreting exosomes containing neurotrophins, growth factors, and anti-inflammatory cytokines that can support photoreceptor survival. Repetitive electromagnetic stimulation (rEMS, Magnovision) modulates ion channels, enhances neuromodulation, and may increase exosome degranulation and iontophoretic delivery of therapeutic molecules. This study aimed to determine whether WJ-MSCs alone or combined with rEMS can slow RP progression compared to natural history over 3 years.
**Methods**
This prospective, sequential, open-label study enrolled 130 eyes of 80 RP patients (mean age ~39 years, various genetic mutations) at Ankara University Faculty of Medicine between January 2019 and December 2022. Patients were divided into four groups: Group 1 (34 eyes, 32 patients) received a single deep subtenon injection of WJ-MSCs (2–6 × 10^6 cells in 1.5 mL); Group 2 (32 eyes, 16 patients) received only rEMS (Magnovision, 2000 milligauss, 42 Hz, 30 min/week for 36 months); Group 3 (32 eyes, 16 patients) received combined WJ-MSCs (once) plus rEMS (starting 10 days later, weekly for 36 months); Group 4 (32 eyes, 16 patients) received no treatment (natural course). All patients took omega-3 supplements. Outcomes were assessed at baseline (T0) and 36 months (T1): fundus autofluorescence surface area (FAF-field), horizontal and vertical ellipsoid zone width (EZW), best-corrected visual acuity (BCVA, ETDRS letters), fundus perimetry deviation index (FPDI, %), and full-field electroretinography magnitude (ERG-m, mV). Statistical analyses used Wilcoxon signed-rank, Kruskal-Wallis, and Mann-Whitney U tests.
**Key Results**
- FAF-field delta changes: Group 1: 0.39 mm² (from 5.99 to 5.60, P=0.01); Group 2: 1.50 mm² (18.4 to 16.9, P=0.04); Group 3: 0.07 mm² (13.35 to 13.28, P=0.41); Group 4: 3.76 mm² (14.13 to 10.37, P=0.01). The 3-year photoreceptor loss rate was 0.5% in Group 3, 7% in Group 1, 9% in Group 2, and 27% in Group 4.
- Horizontal EZW delta: Group 1: 0.20 mm (2.65 to 2.45, P=0.01); Group 2: 0.34 mm (4.18 to 3.84, P=0.01); Group 3: 0.04 mm (3.35 to 3.28, P=0.06); Group 4: 0.86 mm (3.53 to 2.67, P=0.01). Vertical EZW showed similar patterns.
- BCVA delta (letters): Group 1: 3.59 (70.5 to 66.9, P=0.04); Group 2: 4.84 (74.8 to 70.0, P=0.04); Group 3: -0.16 (72.5 to 72.6, P=0.87); Group 4: 12.04 (76.8 to 64.8, P=0.01).
- FPDI delta (%): Group 1: 0.50 (8.3 to 7.8, P=0.03); Group 2: 2.66 (37.6 to 35.0, P=0.04); Group 3: 0.01 (37.5 to 37.5, P=0.96); Group 4: 7.25 (34.6 to 27.4, P=0.01).
- ERG-m delta (mV): Group 1: -0.01 (0.53 to 0.54, P=0.45); Group 2: -0.04 (0.67 to 0.71, P=0.12); Group 3: -0.14 (0.55 to 0.69, P=0.01); Group 4: 0.06 (0.61 to 0.50, P=0.01). The combined group showed significant improvement in ERG-m.
- Between-group comparisons (Kruskal-Wallis) showed significant differences for all parameters (P<0.05), with the combined group consistently demonstrating the least deterioration or improvement.
- No serious ocular or systemic adverse events were reported. Transient foggy vision and light flashes occurred in Group 1 but not in Groups 2 or 3.
**Clinical Implications**
The combination of WJ-MSCs and rEMS (Magnovision) significantly slowed RP progression over 3 years, with a photoreceptor loss rate of only 0.5% compared to 27% in untreated controls. This gene-agnostic approach may offer a safe, non-invasive option to delay vision loss in RP patients, regardless of genetic mutation. The synergistic effect likely arises from rEMS enhancing exosome degranulation, iontophoretic delivery of neurotrophins, and neuromodulation. Limitations include non-randomized group assignment, lack of masking, and heterogeneous genetic mutations. Future studies should include quality-of-life assessments and longer follow-up.