Ocular and Serum Profiles of Inflammatory Molecules Associated With Retinitis Pigmentosa

Overview

Journal Transl Vis Sci Technol

Specialties Biomedical Engineering
Ophthalmology

Date 2024 Aug 9

PMID 39120884

Authors

Yan Tao

Masatoshi Fukushima

Sakurako Shimokawa

Huanyu Zhao

Ayako Okita

Kohta Fujiwara

Atsunobu Takeda

Shizuo Mukai

Koh-Hei Sonoda

Yusuke Murakami

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the profiles and correlations between local and systemic inflammatory molecules in patients with retinitis pigmentosa (RP).

Methods: The paired samples of aqueous humor and serum were collected from 36 eyes of 36 typical patients with RP and 25 eyes of age-matched patients with cataracts. The concentration of cytokines/chemokines was evaluated by a multiplexed immunoarray (Q-Plex). The correlations between ocular and serum inflammatory molecules and their association with visual function were analyzed.

Results: The aqueous levels of IL-6, Eotaxin, GROα, I-309, IL-8, IP-10, MCP-1, MCP-2, RANTES, and TARC were significantly elevated in patients with RP compared to controls (all P < 0.05). The detection rate of aqueous IL-23 was higher in patients with RP (27.8%) compared with controls (0%). In patients with RP, Spearman correlation test demonstrated positive correlations for IL-23, I-309, IL-8, and RANTES between aqueous and serum expression levels (IL-23: ⍴ = 0.8604, P < 0.0001; I-309: ρ = 0.4172, P = 0.0113; IL-8: ρ = 0.3325, P = 0.0476; RANTES: ρ = 0.6685, P < 0.0001). In addition, higher aqueous IL-23 was associated with faster visual acuity loss in 10 patients with RP with detected aqueous IL-23 (ρ = 0.4119 and P = 0.0264). Multiple factor analysis confirmed that aqueous and serum IL-23 were associated with visual acuity loss in patients with RP.

Conclusions: These findings suggest that ocular and systemic inflammatory responses have a close interaction in patients with RP. Further longitudinal studies with larger cohorts are needed to explore the correlation between specific inflammatory pathways and the progression of RP.

Translational Relevance: This study demonstrates the local-systemic interaction of immune responses in patients with RP.

References

Yoshida N, Ikeda Y, Notomi S, Ishikawa K, Murakami Y, Hisatomi T . Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2012; 120(1):e5-12. DOI: 10.1016/j.ophtha.2012.07.008. View

Morizane Y, Morimoto N, Fujiwara A, Kawasaki R, Yamashita H, Ogura Y . Incidence and causes of visual impairment in Japan: the first nation-wide complete enumeration survey of newly certified visually impaired individuals. Jpn J Ophthalmol. 2018; 63(1):26-33. DOI: 10.1007/s10384-018-0623-4. View

Liang L, Peng X, Wang H . Th lymphocyte subsets in patients with Vogt-Koyanagi-Harada disease. Int J Ophthalmol. 2019; 12(2):207-211. PMC: 6376230. DOI: 10.18240/ijo.2019.02.04. View

Zhong Z, Su G, Kijlstra A, Yang P . Activation of the interleukin-23/interleukin-17 signalling pathway in autoinflammatory and autoimmune uveitis. Prog Retin Eye Res. 2020; 80:100866. DOI: 10.1016/j.preteyeres.2020.100866. View

Wilson N, Boniface K, Chan J, McKenzie B, Blumenschein W, Mattson J . Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007; 8(9):950-7. DOI: 10.1038/ni1497. View

Okita A, Murakami Y, Shimokawa S, Funatsu J, Fujiwara K, Nakatake S . Changes of Serum Inflammatory Molecules and Their Relationships with Visual Function in Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2020; 61(11):30. PMC: 7500140. DOI: 10.1167/iovs.61.11.30. View

Ito N, Miura G, Shiko Y, Kawasaki Y, Baba T, Yamamoto S . Progression Rate of Visual Function and Affecting Factors at Different Stages of Retinitis Pigmentosa. Biomed Res Int. 2022; 2022:7204954. PMC: 9303139. DOI: 10.1155/2022/7204954. View

Rangasamy S, McGuire P, Franco Nitta C, Monickaraj F, Oruganti S, Das A . Chemokine mediated monocyte trafficking into the retina: role of inflammation in alteration of the blood-retinal barrier in diabetic retinopathy. PLoS One. 2014; 9(10):e108508. PMC: 4203688. DOI: 10.1371/journal.pone.0108508. View

Ghoreschi K, Balato A, Enerback C, Sabat R . Therapeutics targeting the IL-23 and IL-17 pathway in psoriasis. Lancet. 2021; 397(10275):754-766. DOI: 10.1016/S0140-6736(21)00184-7. View

10.

Murakami Y, Yoshida N, Ikeda Y, Nakatake S, Fujiwara K, Notomi S . Relationship between aqueous flare and visual function in retinitis pigmentosa. Am J Ophthalmol. 2015; 159(5):958-63.e1. DOI: 10.1016/j.ajo.2015.02.001. View

11.

Hartong D, Berson E, Dryja T . Retinitis pigmentosa. Lancet. 2006; 368(9549):1795-809. DOI: 10.1016/S0140-6736(06)69740-7. View

12.

Hata M, Andriessen E, Hata M, Diaz-Marin R, Fournier F, Crespo-Garcia S . Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation. Science. 2023; 379(6627):45-62. DOI: 10.1126/science.abj8894. View

13.

Ghasemi H, Ghazanfari T, Yaraee R, Faghihzadeh S, Hassan Z . Roles of IL-8 in ocular inflammations: a review. Ocul Immunol Inflamm. 2011; 19(6):401-12. DOI: 10.3109/09273948.2011.618902. View

14.

Blauvelt A, Chiricozzi A . The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis. Clin Rev Allergy Immunol. 2018; 55(3):379-390. PMC: 6244934. DOI: 10.1007/s12016-018-8702-3. View

15.

Yoshida N, Ikeda Y, Notomi S, Ishikawa K, Murakami Y, Hisatomi T . Clinical evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology. 2012; 120(1):100-5. DOI: 10.1016/j.ophtha.2012.07.006. View

16.

Funatsu J, Murakami Y, Shimokawa S, Nakatake S, Fujiwara K, Okita A . Circulating inflammatory monocytes oppose microglia and contribute to cone cell death in retinitis pigmentosa. PNAS Nexus. 2022; 1(1). PMC: 9075747. DOI: 10.1093/pnasnexus/pgac003. View

17.

Murakami Y, Ikeda Y, Nakatake S, Fujiwara K, Tachibana T, Yoshida N . C-Reactive protein and progression of vision loss in retinitis pigmentosa. Acta Ophthalmol. 2017; 96(2):e174-e179. DOI: 10.1111/aos.13502. View

18.

Lu B, Yin H, Tang Q, Wang W, Luo C, Chen X . Multiple cytokine analyses of aqueous humor from the patients with retinitis pigmentosa. Cytokine. 2019; 127:154943. DOI: 10.1016/j.cyto.2019.154943. View

19.

Olivares-Gonzalez L, Velasco S, Campillo I, Rodrigo R . Retinal Inflammation, Cell Death and Inherited Retinal Dystrophies. Int J Mol Sci. 2021; 22(4). PMC: 7924201. DOI: 10.3390/ijms22042096. View

20.

Elner V, Elner S, Standiford T, Lukacs N, Strieter R, Kunkel S . Interleukin-7 (IL-7) induces retinal pigment epithelial cell MCP-1 and IL-8. Exp Eye Res. 1996; 63(3):297-303. DOI: 10.1006/exer.1996.0118. View