Therapeutic efficacy of tofacitinib in PDSAg-induced chronic experimental autoimmune uveitis in Wistar rat
Immunopharmacology and Immunotoxicology, cilt.47, sa.4, ss.476-484, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 47 Sayı: 4
- Basım Tarihi: 2025
- Doi Numarası: 10.1080/08923973.2025.2508278
- Dergi Adı: Immunopharmacology and Immunotoxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
- Sayfa Sayıları: ss.476-484
- Anahtar Kelimeler: Experimental autoimmune uveitis, JAK inhibitor, PDSAg, tofacitinib, Wistar rat
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Purpose: Tofacitinib, a small molecule pan-JAK inhibitor, targets key inflammatory pathways that play a pivotal role in the pathophysiology of uveitis. Its ability to inhibit multiple cytokine signaling pathways makes it a promising candidate for the treatment of ocular inflammation. This study aimed to investigate the effect of oral tofacitinib on peptide-derived S-antigen (PDSAg)-induced chronic experimental autoimmune uveitis (EAU) in rats. Materials and methods: Nineteen albino Wistar rats were divided into five groups. Groups 1–3 (5 rats each) were immunized with 15 micrograms PDSAg to induce EAU; Group 2 received tofacitinib (5 mg/kg) by gavage twice daily. Group 3 received saline in the same manner as Group 2. Group 4 (2 rats) was a healthy control group. Group 5 (2 rats) received only tofacitinib. Uveitis development and treatment efficacy were evaluated using clinical scoring based on the the signs of anterior segment inflammation and histological scoring based on the deterioration of the retinal architectural structure. Results: Uveitis confirmed based on histological evidence was observed in all EAU groups (Groups 1–3) compared to the healthy control group (Group 4) (p < 0.001, Mann-Whitney U test). Tofacitinib significantly delayed the onset of uveitis in Group 2 when compared with Groups 1 and 3, which did not receive tofacitinib (p < 0.001, Mann-Whitney U test). Histological scores also showed a trend toward reduction (p = 0.393, Mann-Whitney U test). Conclusions: Oral tofacitinib delayed uveitis onset and reduced clinical and histological findings, suggesting its potential as an alternative treatment for uveitis.