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Original Article
Online Published: 30 Jul 2026
 


Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model

Rana A. Abdelkhalek, Marwa A. Fouly, Mohamed M. Bahr, Amal E. Ibrahim, Islam Elgohary, Ashraf Shamaa.


Abstract
Abstract
This study evaluated the short term ocular safety and tolerability of mesenchymal stem cell-derived extracellular vesicles (MSC-Evs) following a single intravitreal injection at a moderate, safety-oriented dose in a rabbit model. Twelve male adult New Zealand white rabbits were allocated randomly into two groups (n = 6 per group). The group I received 0.05 mL of sterile distilled water injected intravitreally, on the other hand group II received 2.5 × 10⁸ particles of MSC-Evs in 0.05 mL per eye. Only single eye per rabbit was injected, while the contralateral eye acted as group III. Retinal structure and function were assessed through spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), respectively, at baseline and at two-week intervals for six weeks study period. Histopathological and immunohistochemical assessments were performed on the retina at study termination. ERG analysis revealed no significant differences in a- wave and b- wave amplitudes or implicit times among groups. SD-OCT demonstrated stable retinal architecture, with no evidence of retinal edema, degeneration or alteration in retinal thickness in injected eyes compared to controls. These data were supported by statistical analysis (P > 0.05, two-way repeated-measured ANOVA). Histopathology showed no necrosis, inflammatory infiltrates, or retinal thinning, while caspase-3 immunohistochemical analysis showed no increase in apoptotic labeling. A single intravitreal injection of MSC-Evs )2.5 x108 particles/eye) was well tolerated in rabbits over six weeks with no evidence of functional or structural retinal toxicity. These findings support the short-term ocular safety of intravitreal MSC-Evs administration and provide a preclinical safety standard for future dose finding and efficacy studies in retinal disease.

Key words: Exosomes; Mesenchymal-Stem-Cells; Extracellular-Vesicles; Intravitreal-Injections; Ocular Safety


 
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How to Cite this Article
Pubmed Style

Abdelkhalek RA, Fouly MA, Bahr MM, Ibrahim AE, Elgohary I, Shamaa A. Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. AJVS. Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919

Web Style

Abdelkhalek RA, Fouly MA, Bahr MM, Ibrahim AE, Elgohary I, Shamaa A. Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. https://www.alexjvs.com/?mno=323919 [Access: July 30, 2026]. doi:10.5455/ajvs.323919

AMA (American Medical Association) Style

Abdelkhalek RA, Fouly MA, Bahr MM, Ibrahim AE, Elgohary I, Shamaa A. Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. AJVS. Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919


Vancouver/ICMJE Style

Abdelkhalek RA, Fouly MA, Bahr MM, Ibrahim AE, Elgohary I, Shamaa A. Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. AJVS, [cited July 30, 2026]; Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919


Harvard Style

Abdelkhalek, R. A., Fouly, . M. A., Bahr, . M. M., Ibrahim, . A. E., Elgohary, . I. & Shamaa, . A. (0) Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. AJVS, Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919


Turabian Style

Abdelkhalek, Rana A., Marwa A. Fouly, Mohamed M. Bahr, Amal E. Ibrahim, Islam Elgohary, and Ashraf Shamaa. 0. Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. Alexandria Journal of Veterinary Sciences, Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919


Chicago Style

Abdelkhalek, Rana A., Marwa A. Fouly, Mohamed M. Bahr, Amal E. Ibrahim, Islam Elgohary, and Ashraf Shamaa. "Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model." Alexandria Journal of Veterinary Sciences Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919


MLA (The Modern Language Association) Style

Abdelkhalek, Rana A., Marwa A. Fouly, Mohamed M. Bahr, Amal E. Ibrahim, Islam Elgohary, and Ashraf Shamaa. "Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model." Alexandria Journal of Veterinary Sciences Online First: 30 Jul, 2026. Web. 30 Jul 2026 doi:10.5455/ajvs.323919


APA (American Psychological Association) Style

Abdelkhalek, R. A., Fouly, . M. A., Bahr, . M. M., Ibrahim, . A. E., Elgohary, . I. & Shamaa, . A. (0) Short-Term Acute Ocular Safety and Tolerability of Intravitreal Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Rabbit Model. Alexandria Journal of Veterinary Sciences, Online First: 30 Jul, 2026. doi:10.5455/ajvs.323919




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    Egypt.

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