Intravitreal mesenchymal stem cells are safe and well-tolerated in pigmented-rabbit eyes

Abstract

Purpose: To evaluate safety and tolerance of intravitreally-injected mesenchymal stem cells in pigmented-rabbit eyes, by ophthalmic follow-up and histological study

Methods: Mesenchymal stem cells used in this study (MSV; Citospin SL, Valladolid, Spain) are approved for clinical used by the Spanish Drug Agency (PEI n010-134). Twelve rabbits (Rex Chinchilla-NZW) were randomized into three groups of 4 animals. Groups 1 and 2 received an intravitreal injection into the right eye of 1.5x10⁶ and 0.75x10⁶ MSV, respectively, in 0.05 mL vehicle (Ringer-Lactato-based). In Group 3 (control) only the vehicle was injected. Evaluation of anterior pole by slit-lamp, posterior pole by inverted ophthalmoscopy and intraocular pressure by Tonopen® were performed. Clinical signs were evaluated before MSV injection and weekly during 6 weeks. Clinical findings were graded and scored by the Hackett&McDonald method. Finally, animals were sacrificed and the eyes, liver, spleen and gonads processed for hematoxylin and eosin (HE) and periodic acid of Shiff (PAS) staining and histological evaluation

Results: Clinical data did not show statistical significance between control and MSV-injected rabbit eyes at any time point evaluated (p<0.05). No relevant histological findings related to ocular, liver, spleen and/or gonads modifications were observed in any group. MSV were detected intraocularly in only one animal of the Group 1 at 6 weeks

Conclusions: Mesenchymal stem cells (MSV) are safe and well tolerated after intravitreal injection in pigmented-rabbit eyes. Further studies are necessary to evaluate persistence, distribution and potential extraocular migration