Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton's Jelly Derived Mesenchymal Stem Cells

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between photoreceptor cells and choroidal blood vessels. Photoreceptor cells are vitally and functionally dependent on the RPE. The conversion of blood glucose to ATP, synthesis of proteins in the visual cycle and removal of metabolic waste takes place in the RPE. For these important processes, various peptide growth factors and their receptors are synthesized in the RPE. More than 260 genes in the RPE are responsible for the production of these peptide fragments. Mutations in any of these genes as well as ischemic, physical or chemical RPE damage causes retinal degeneration. Retinal degeneration may be inherited, such as in retinitis pigmentosa (RP), Stargardt's disease, choroideremia, Best vitelliform dystrophy and Bietti's crystalline dystrophy. Retinal degeneration may also be acquired through genetic mechanisms, such as age-releated macular degeneration. In retinal degeneration, there is a developing loss of RPE and photoreceptors, regardless of the underlying cause.

Umbilical cord Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) have significant paracrine and immunomodulatory properties. WJ-MSCs secrete trophic factors that stimulate RPE or secrete trophic factors that are similar to those produced by RPE. In studies using animal models, WJ-MSCs have been found to be effective in stopping the progression of retinal degeneration and for rescuing photoreceptors in the dormant phase. WJ-MSCs are hypoimmunogenic and have significant immunomodulatory properties. WJ-MSCs have been shown to suppress chronic inflammation and prevent apoptosis in animal models of neurodegenerative and ischemic retinal disorders. WJ-MSCs also stimulate progenitor cells in the retina and elicit self-repair mechanisms.

The aim of this preliminary clinical study is to investigate the efficacy of deep sub-tenon injected WJ-MSCs as a stem cell treatment modality for the management of retinitis pigmentosa, which creates outer retinal degeneration. These functional and structural effects were investigated using microperimetry, electrophysiology and spectral domain optical coherence tomography (SD-OCT). To the best of our knowledge, this is the first prospective clinical study that utilizes a large number of RP cases, and cases that are in phase-3.

Inclusion criteria

• • 18 years of age or older;

• Diagnosis of any phenotypic or genotypic variation of RP, confirmed by clinical history, fundus appearance, visual field (VF), electroretinogram (ERG) and genetic mutation analysis;
• Having experienced various degrees of VF loss;
• BCVA from 50 letters to 110 letters in the ETDRS chart testing (Topcon CC-100 XP, Japan);
• Mean deviation (MD) values ranging between -33.0 and -5.0 dB with Compass visual field analysis (threshold 24-2, Sita Standard, Stimulus 3-white);
• Intraocular pressure (IOP) of <22 mmHg.

Exclusion criteria

• • The presence of cataracts or other media opacity that might affect the VF, MD, or ERG recordings;

• The presence of glaucoma, which causes visual field and optic disc changes;
• The presence of any systemic disorder (e.g.,diabetes, neurological disease, or uncontrolled systemic hypertension) that may affect visual function;
• The habit of smoking.