Contents lists available at ScienceDirect Experimental Eye Research journal homepage: www.elsevier.com/locate/yexer pH balance and lactic acid increase in the vitreous body of diabetes mellitus patients Hiroki Mieno a , Yoshinori Marunaka b,c,d,e,* , Tohru Inaba f , Kentaro Kojima a , Kazuhito Yoneda a , Kenji Nagata a , Chie Sotozono a a Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan b Research Institute for Clinical Physiology, Kyoto Industrial Health Association, Kyoto, Japan c Research Center for Drug Discovery and Pharmaceutical Development Science, Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Japan d Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine, Kyoto, Japan e International Research Center for Food Nutrition and Safety, College of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China f Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan ARTICLE INFO Keywords: pH Vitreous body Diabetes mellitus Lactate Ca 2+ ABSTRACT Although there have been no previous reports on the pH of the human vitreous body, it has been highly theorized that it changes in patients with diabetes mellitus (DM). In humans, it is necessary to measure the vitreous pH in vitro, which is an important point that presents a major problem, as vitreous pH immediately changes when exposed to air. The purpose of this present study was to report our recent development of an in vitro method for measuring vitreous pH via the combination of 27-gauge (G) vitreous surgery and a blood gas analyzer, as well as our investigative findings on whether or not there is a difference of pH depending on the presence of diabetes mellitus (DM). This cross-sectional study involved 30 subjects [18 subjects without DM (DM-) and 12 subjects with DM (DM+)] with no previous history of ophthalmologic surgery. The DM+ group included 6 cases of proliferative diabetic retinopathy (PDR) and 6 cases of non-PDR (NPDR). The DM- Group was comprised of patients with a macular hole or idiopathic epiretinal membrane. The DM+ Group included patients not only with macular hole or idiopathic epiretinal membrane but also diabetic macular edema, however, patients with obvious vitreous hemorrhage were excluded. In all patients, a vitreous specimen was anaerobically obtained at the start of 27G pars plana vitrectomy, with a venous blood sample being collected immediately prior to surgery. Between the DM- and DM+ subjects, pH, partial pressure of carbon dioxide (pCO 2) , partial pressure of oxygen (pO 2 ), K + , Na + , Ca 2+ , Cl - , lactate, and glucose were compared. In the items in which a significant difference was found between DM- and DM+, the values between the PDR and NPDR cases were also compared. Our findings showed no significant difference in vitreous and venous-blood pH between the DM- and DM+ subjects. The vitreous biochemical data revealed that Ca 2+ significantly reduced and lactate and glucose significantly increased in DM+ compared to DM-. Thus, we compared Ca 2+ , lactate, and glucose between the PDR and NPDR cases. Although glucose did not significantly change, Ca 2+ significantly decreased and lactate significantly in- creased in the PDR cases. The venous biochemical data revealed that only glucose significantly increased in DM +. The data in all investigated items was found to be significantly different between the vitreous and venous samples. Our findings revealed that lactate increases and Ca 2+ decreases in the vitreous body of DM patients, especially those with PDR, probably due to the increased production of lactic acid. However, although the production of lactic acid increased, the pH remained at a nearly constant value, thus suggesting that the human vitreous body has a high buffering capacity. 1. Introduction It is widely known that pH is an indispensable indicator for judging homeostasis in the body. In the human body, blood has powerful pH buffering molecules, such as hemoglobin and albumin, and the pH of blood strictly stays at a pH-scale range of between 7.35 and 7.45. Conversely, in our previously reported studies, we discovered that the pH of interstitial fluids is highly variable due to the fact that those fluids https://doi.org/10.1016/j.exer.2019.107789 Received 19 May 2019; Received in revised form 30 August 2019; Accepted 2 September 2019 * Corresponding author. Research Institute for Clinical Physiology, Kyoto Industrial Health Association, 67 Kitatsuboi-cho, Nishinokyo, Nakagyo-ku, Kyoto, 604- 8472, Japan. E-mail address: marunaka@koto.kpu-m.ac.jp (Y. Marunaka). Experimental Eye Research 188 (2019) 107789 Available online 03 September 2019 0014-4835/ © 2019 Elsevier Ltd. All rights reserved. T