Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects

Paolo Giuseppe Limoli, Celeste Silvana Serena Limoli, Marco Ulises Morales, Enzo Maria Vingolo, Paolo Giuseppe Limoli, Celeste Silvana Serena Limoli, Marco Ulises Morales, Enzo Maria Vingolo

Abstract

Purpose: To assess whether treatment with the Limoli Retinal Restoration Technique (LRRT) can be performed in patients with retinitis pigmentosa (RP), grafting the autologous cells in a deep scleral pocket above the choroid of each eye to exert their beneficial effect on the residual retinal cells.

Methods: The patients were subjected to a complete ophthalmological examination, including best corrected visual acuity (BCVA), close-up visus measurements, spectral domain-optical coherence tomography (SD-OCT), microperimetry (MY), and electroretinography (ERG). Furthermore, the complete ophthalmological examination was carried out at baseline (T0) and at 6 months (T180) after surgery. The Shapiro-Wilk test was used to assess the normality of distribution of the investigated parameters. A mixed linear regression model was used to analyse the difference in all the studied parameters at T0 and T180, and to compare the mean change between the two groups. All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA).

Results: LRRT treatment was performed in 34 eyes of 25 RP patients recruited for the study. The eyes were classified in two groups on the basis of foveal thickness (FT) assessed by SD-OCT: 14 eyes in Group A (FT≤190μm) and the remaining 20 ones in Group B (FT > 190μm). Although it had not reached the statistical significance, Group B showed a better improvement in BCVA, residual close-up visus and sensitivity than Group A.

Conclusions: Previous studies have described the role of LRRT in slowing down retinal degenerative diseases. Consequently, this surgical procedure could improve the clinical and rehabilitative prognostic parameters in RP patients. On the other hand, further clinical research and studies with longer follow-up will be needed to evaluate its efficacy.

Keywords: Autograft; Limoli retinal restoration technique (LRRT); cell surgery; embryonic stem cells (ESC); foveal thickness; growth factor (GF); induced pluripotent stem cells (iPSCs); mesenchymal cell (MSC); retinitis pigmentosa (RP).

Figures

Fig. 1
Fig. 1
The suprachoroidal autograft obtained by Limoli Retinal Restoration Technique (LRRT) allows placing fat stromal cells, adipose tissue-derived stem cells (ADSCs) and platelets (PLTs) obtained from PLT-rich plasma (PRP) close to the choroid. The production of growth factors (GF), characteristic of these cells, is poured directly into the choroidal flow, helping to maintain retinal cell trophism. The GFs, through the choroidal flow, have a direct action on the choroid, on the Müller cells, on the retinal pigment epithelium (RPE) cells with improvement of physiology of the outer segments (OS), on the rods and on the cones.
Fig. 2
Fig. 2
The best corrected visual acuity (BCVA) was stable after suprachoroidal autograft with Limoli Retinal Restoration Technique (LRRT), or increased (+16.31%) in patients with foveal thickness (FT) >190μm.
Fig. 3
Fig. 3
Residual Close-Up Visus change post Limoli Retinal Restoration Technique (LRRT) depending on foveal thickness. Six months after surgery (T180) the close-up visus was stable if the foveal thickness (FT) ≤190μm or increased by +22.46% in the group where the FT was >190μm.
Fig. 4
Fig. 4
After stem cell surgery, Limoli Retinal Restoration Technique (LRRT), at 6 months (T180) there was a more relevant change for sensitivity in the group with foveal thickness >190μm (Group B), recorded with microperimetry.
Fig. 5
Fig. 5
A thin foveal thickness (FT) μm (Group A), as computed in our study, means that the retinal cell population is small, foveal structures are often dystrophic and the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex is no longer recognizable. Retinitis pigmentosa (RP). Limoli Retinal Restoration Technique (LRRT).
Fig. 6
Fig. 6
A considerable foveal thickness (FT) >190μm (Group B), as computed in our study, means that the retinal cell population is still large, foveal structures are still intact and the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex is recognizable. Mesenchymal cell administration showed the ability to exert a positive influence over functional parameters six months after Limoli Retinal Restoration Technique (LRRT). Retinitis pigmentosa (RP). Photopic electroretinogram (cERG).
Fig. 7
Fig. 7
The average threshold of close-up visus with magnifying system did not show a statistically significant change after cell surgery.
Fig. 8
Fig. 8
Compliance analysis of retinitis pigmentosa (RP) patients at 6 months (T180) post Limoli Retinal Restoration Technique (LRRT) depending on foveal thickness: compliance was good in 73.53% of all cases (both Groups A and B). Patients reported to see better 6 months after surgery, but the percentage reached 90% in those with FT > 190μm. If we considered only the improved group (25 eyes), 18 eyes (72%) belonged to Group B and 7 eyes (28%) to Group A.

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