Authors
Ali Khodor, Symon Ma, Seitaro Komai, Yasufumi Tomioka, Carolina Moreira Dos Santos, Leonardo L de Castro, Gabriella C Mezzich, Manuel E Quiroga-Garza, Raul E Ruiz-Lozano, Hazem Mousa, Hon Shing Ong, Andri K Riau, Sejiro Littleton, Mayumi Ueta, Jodhbir S Mehta, Daniel R Saban, Victor L Perez
Published in
Investigative ophthalmology & visual science. Volume 67. Issue 8. Pages 44. Jul 01, 2026.
Abstract
To test the therapeutic potential of mesenchymal stem cell-derived exosomes (MSC-exos) in ocular surface inflammation and to characterize immune responses in an IKAROS family zinc finger (IKZF) murine model of Stevens-Johnson syndrome (SJS) with allergic eye disease (AED).
Transgenic mice expressing IKZF1 were used as the SJS model. To induce ocular surface inflammation, the mice were immunized with intraperitoneal ovalbumin in aluminum hydroxide (alum) and pertussis toxin and challenged with topical ovalbumin. Conjunctival tissues and draining lymph nodes (LNs) were analyzed by flow cytometry to characterize immune responses. MSC-exos were prepared from immortalized human embryonic stem cell-derived MSCs. Clinical disease was evaluated daily. The pharmacokinetics of Alexa Fluor 488-labeled MSC-exos were tracked using in vivo multiphoton confocal microscopy.
IKZF mice demonstrated increased conjunctival immune cell infiltration compared with wild-type controls, which was further amplified following allergic challenge. IKZF+AED mice exhibited expansion of innate and adaptive populations in the conjunctiva. Draining LNs showed increased frequencies of cytokine-producing CD4⁺ T cells. MSC-exo treatment significantly reduced clinical disease severity, with subconjunctival administration producing the greatest improvement, comparable to corticosteroid therapy. Pharmacokinetic imaging demonstrated rapid clearance of topically administered exosomes, whereas subconjunctival delivery resulted in retention within ocular tissues for up to 72 hours and localization within the conjunctival stroma.
The IKZF+AED model demonstrates local conjunctival inflammation and systemic T-cell activation consistent with SJS-associated ocular disease. MSC-exos significantly improved clinical inflammation, and their therapeutic efficacy was strongly influenced by delivery route. Prolonged tissue retention following subconjunctival administration suggests that pharmacokinetic exposure within conjunctival tissues may be a key determinant of therapeutic effect.
PMID:
42479023
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.
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