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Morio Ueno, Munetoyo Toda, Asako Hiraga, Koichi Wakimasu, Noriko Koizumi, Naoki Okumura, Kazuko Asada, Chie Sotozono, Junji Hamuro, Shigeru Kinoshita; Profiles of cytokines in the aqueous humor and serum of bullous keratopathy patients. Invest. Ophthalmol. Vis. Sci. 2016;57(12):898. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We are currently developing novel form of regenerative medicine for bullous keratopathy (BK) involving cultivated human corneal endothelial cells (HCECs). Although transplanted cells hold promise for treating BK by ‘seeding’ corneal endothelium, the regenerative ability of injected cells would be influenced by the anterior chamber (AC) milieu. The purpose of this study was to examine cytokine profiles in the aqueous humor (AH) and serum of BK patients to elucidate the contribution of AC milieu to a successful surgical outcome.
Serum was obtained from BK patients before and after undergoing cell therapy. AH samples were obtained at the start of the surgical procedure from patients undergoing cell-injection therapy or Descemet's stripping automated endothelial keratoplasty (DSAEK). Bio-Plex® Multiplex Immunoassay (Bio-Rad Laboratories) was used to measure the concentrations of 27 cytokines.
IL-1ra, IL-6, IL-7, IL-8, IL-10, IL-12, IL-15, bFGF, Eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1β, RANTES, TNF-α, and VEGF were detected in all AH samples. AH cytokine levels from BK patients before cellinjection therapy were comparable to those from BK patients before DSAEK. Cytokine profiles were classified into 3 distinct patterns: 1) increment of GM-CSF alone, 2) increment of GM-CSF and MCP-1, and 3) increment of GM-CSF, MCP-1, and MIP-1β. RANTES, TNF-α, and VEGF were elevated in 6 BK patients before cell injection, indicating ongoing low-level persistent inflammation in the AC of BK patients. Variation in serum cytokine levels was also found among BK patients before surgery. Our recent findings revealed that cultivated HCECs are composed of diverse subpopulations in regard to the expression of CD44. Different patterns of periodical changes of serum cytokines were observed between cell therapy with CD44- and CD44+ cultivated HCECs. Serum cytokine levels were elevated and remained high for 2 weeks post injection of CD44+ cultivated HCECs, while little changes were confirmed post injection of CD44- cultivated HCECs. Serum cytokine levels were recovered in 2 months in all cases.
AH cytokines might be biomarkers to reveal BK pathogenesis. CD44- fully differentiated cultivated HCECs may not perturb cytokine milieu in AH post cell-injection therapy, and the absence of local inflammation might be linked to successful survival of the injected cells.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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