Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Autor: Choi H; Konkuk-KIST Biomedical Science & Technology, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Lee HE; Department of Veterinary Ophthalmology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Lee SV; Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Joo JS; Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Baek H; Konkuk-KIST Biomedical Science & Technology, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Kim S; Department of Obstetrics and Gynecology, Sang-Gye Paik Hospital, Inje University School of Medicine, 1342 Dongil-ro, Nowon-gu, Seoul, 01757, Republic of Korea., Park M; Konkuk-KIST Biomedical Science & Technology, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Lee SW; Department of Veterinary Microbiology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea; Veterinary Science Research Institute, KU Research Center for Zoonosis, KU Center for Animal Blood Medical Science Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Yang SW; Department of Obstetrics and Gynecology, Sang-Gye Paik Hospital, Inje University School of Medicine, 1342 Dongil-ro, Nowon-gu, Seoul, 01757, Republic of Korea., Hwang HS; Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, Research Institute of Medical Science, Konkuk University School of Medicine, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea., Kim JY; Department of Veterinary Ophthalmology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. Electronic address: canvet@konkuk.ac.kr., Kang YS; Konkuk-KIST Biomedical Science & Technology, Konkuk University, 120, Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea; Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea; Veterinary Science Research Institute, KU Research Center for Zoonosis, KU Center for Animal Blood Medical Science Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea. Electronic address: kangyo67@konkuk.ac.kr.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2024 Mar; Vol. 240, pp. 109782. Date of Electronic Publication: 2024 Jan 09.
DOI: 10.1016/j.exer.2024.109782
Abstrakt: Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1β, MMP9, IL-10, TGF-β, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1β, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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