Higher Intraocular Levels of Inflammatory Factors are Related to Retinal Vascular and Neurodegeneration in Myopic Retinopathy

Ling Zeng,1– 4 Zhikuan Yang,1– 3 Wei Pan,1,3 Ding Lin,2 Yao Tang,1– 3 Baihua Chen,4 Heping Xu,1,3,5 Xiaoning Li1– 3,6 1Aier Academy of Ophthalmology, Central South University, Changsha, People’s Republic of China; 2Changsha Aier Eye Hospital, Changsha, People’s Republic of China; 3Aier Institute of Optometry and Vision Science, Aier Eye Hospital Group, Changsha, People’s Republic of China; 4The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 6Aier School of Optometry and Vision Science, Hubei University of Science and Technology, Xianning, People’s Republic of ChinaCorrespondence: Heping Xu; Xiaoning Li, Tel +44(0)28909 76463, Email [email protected]; [email protected]: In this study, we aimed to investigate the relationship between the intraocular levels of inflammatory factors and myopia-related retinal vascular and neuronal degeneration.Patients and Methods: One hundred and forty-seven patients with Implantable Collamer Lens (ICL) implantation were enrolled and all participants received comprehensive ophthalmic examination. About 100~150 ul of aqueous humor was collected immediately before ICL surgery. The levels of inflammatory factors including Aggrecan, April, BAFF, CCL5, CD163, Chi3l1, gp130, IL-6Rα, IL-8, IL-10, IL-11, IL-12, IL-19, IL-27, IL-28A, IL-34, IFN-β, IFN-γ, MMP-1, MMP-2, MMP-3 and PTX3 in the aqueous humor were measured using the Luminex Multiplexing system.Results: Results showed that aqueous humor levels of pro-inflammatory factors Chi3l1, IL-6Rα, IL-8, IL-12, IL-27, inflammation-related cytokines April, BAFF and IL-34 progressively increased from the progression of myopic retinopathy. Conversely, the aqueous levels of IL-11 and Aggrecan gradually decreased from the progression of myopic retinopathy. Correlation analysis showed that the intraocular levels of Chi3l1, IL-6Rα, IL-8, IL-27 and BAFF were negatively correlated with retinal vascular density. The intraocular level of IL-6Rα was negatively correlated with retinal neuronal thickness. Protein–Protein Interaction (PPI) analysis revealed that Chi3l1 and Aggrecan were the upstream cytokines that affect IL-10 and IL-8 in the pathological myopic eyes. KEGG pathway analysis showed that cytokine–cytokine receptor interaction, JAK-STAT signaling pathway, rheumatoid arthritis, and chagas disease were influenced by these altered inflammatory factors (adjusted p-value< 0.001).Conclusion: The production of inflammatory factors in the eyes of individuals with high myopia and pathological myopia was altered, and the elevated levels of intraocular pro-inflammatory factors such as Chi3l1, IL-6Rα, and IL-8 were closely associated with myopia-related retinal microvascular and neurodegeneration.Keywords: aqueous humor, inflammation, posterior staphyloma, myopic chorioretinal atrophy