Noncontact optical device for measuring blood glucose in aqueous humor: a pilot clinical study investigating correlation with blood glucose levels.

Significance: Monitoring blood glucose levels is crucial for individuals with diabetes. Noninvasive methods for measuring serum glucose levels have been explored to aid in blood glucose control for diabetes management. Aim: We introduced a noncontact optical glucometer (NCGM) for measuring glucose levels in the aqueous humor of the human eye. We also investigated the correlation between glucose levels in the NCGM and the aqueous humor, blood samples, and self-monitoring blood glucose devices. Approach: The optical system used in this study measured both the near-infrared absorption and polarized rotatory distribution of glucose molecules in the human aqueous humor. This prospective study's outcomes were eye aqueous glucose level, preoperative blood glucose level, intraoperative blood glucose level, and NCGM reading of patients in a single center in Taiwan. Results: The NCGM's measurements showed a strong correlation with blood glucose levels (intra-class correlation [ICC]: 0.95 to 0.98) and aqueous humor glucose levels (ICC: 0.76), indicating its ability to noninvasively measure blood glucose levels in human subjects. Conclusions: This NCGM may offer a convenient, pain-free, and rapid tool for measuring blood glucose levels in diabetic patients. The device could represent a significant advancement in noncontact hybrid optical glucose measurement systems.

Noncontact Optical Measurement of Aqueous Humor Glucose Levels and Correlation with Serum Glucose Levels in Rabbit.

The noninvasive measurement of serum glucose levels has been investigated for the monitoring of blood sugar control in diabetes. In our study, we aimed to develop a novel noncontact glucometer (NCGM) utilizing an optical approach to measure the intraocular aqueous humor glucose levels in the anterior chamber of rabbit eyes. The NCGM consists of a hybrid optical system that simultaneously measures near-infrared absorption and the polarized rotatory distribution of glucose molecules in the aqueous humor. In vitro optical measurements demonstrated that NCGM measurements had high precision and repeatability for different glucose levels, including 50 mg/dL (14.36%), 100 mg/dL (-4.05%), 200 mg/dL (-5.99%), 300 mg/dL (4.86%), 400 mg/dL (-2.84%), 500 mg/dL (-0.11%), and 600 mg/dL (4.48%). In the rabbit experiments, we found a high correlation between aqueous glucose levels and serum glucose levels, with a mean difference of 8 mg/dL. According to the testing results, the in vivo NCGM measurement of aqueous humor glucose levels also displayed a high correlation with serum glucose levels, with a mean difference of 29.2 mg/dL. In conclusion, aqueous humor glucose levels were accurately measured using the NCGM, and the results correlated with serum glucose levels.

Inhibiting TLR7 Expression in the Retinal Pigment Epithelium Suppresses Experimental Autoimmune Uveitis.

Experimental autoimmune uveitis (EAU), a model of human uveitis, is an organ-specific, T cell-mediated autoimmune disease. Autoreactive T cells can penetrate the blood-retinal barrier, which is a physical defense composed of tight junction-linked retinal pigment epithelial (RPE) cells. RPE cells serve as antigen-presenting cells (APCs) in the eye since they express MHC class I and II and Toll-like receptors (TLRs). Although previous studies have shown that supplementation with TLR agonists exacerbates uveitis, little is known about how TLR signaling in the RPE contributes to the development of uveitis. In this study, we isolated the RPE from EAU mice, which were induced by active immunization (aEAU) or adoptive transfer of antigen-specific T cells (tEAU). The expression of TLRs on RPE was determined, and both aEAU and tEAU mice exhibited induced tlr7 expression. The TLR7 agonist R848 was shown to induce aggressive disease progression, along with significantly elevated levels of the uveopathogenic cytokine IL-17. Furthermore, not only IL-17 but also R848 appeared to enhance the inflammatory response and to impair the barrier function of the RPE, indicating that TLR7 signaling is involved in the pathogenesis of EAU by affecting the behaviors of the RPE and consequently allowing the infiltration of autoreactive T cells intraocularly. Finally, local application of shRNA against TLR7 delivered by recombinant AAV effectively inhibited disease severity and reduced IFN-γ and IL-17. Our findings highlight an immunomodulatory role of RPE TLR7 in EAU development and provide a potential therapeutic strategy for autoimmune uveitis.

Interleukin-4 Supports the Suppressive Immune Responses Elicited by Regulatory T Cells.

Interleukin-4 (IL-4) has been considered as one of the tolerogenic cytokines in many autoimmune animal models and clinical settings. Despite its role in antagonizing pathogenic Th1 responses, little is known about whether IL-4 possesses functions that affect regulatory T cells (Tregs). Tregs are specialized cells responsible for the maintenance of peripheral tolerance through their immune modulatory capabilities. Interestingly, it has been suggested that IL-4 supplement at a high concentration protects responder T cells (Tresps) from Treg-mediated immune suppression. In addition, such supplement also impedes TGF-ß-induced Treg differentiation in vitro. However, these phenomena may contradict the tolerogenic role of IL-4, and the effects of IL-4 on Tregs are therefore needed to be further elucidated. In this study, we utilized IL-4 knockout (KO) mice to validate the role of IL-4 on Treg-mediated immune suppression. Although IL-4 KO and control animals harbor similar frequencies of Tregs, Tregs from IL-4 KO mice weakly suppressed autologous Tresp activation. In addition, IL-4 deprivation impaired the ability of Tregs to modulate immune response, whereas IL-4 supplementation reinforced IL-4 KO Tregs in their function in suppressing Tresps. Finally, the presence of IL-4 was associated with increased cell survival and granzyme expression of Tregs. These results suggest the essential role of IL-4 in supporting Treg-mediated immune suppression, which may benefit the development of therapeutic strategies for autoimmune diseases.

Relationship between the maxillary transverse dimension and palatally displaced canines: A cone-beam computed tomographic study.

OBJECTIVES: To examine the relationship between palatally displaced maxillary canines (PDC) and the maxillary transverse dimension using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Thirty-three patients (11 males and 22 females, mean age 18.2 years) with PDC were matched to 66 patients (22 males and 44 females, mean age 18.1 years) without PDC (control) by gender, age, and posterior occlusion. A CBCT image was taken on all the patients prior to any orthodontic treatment. For each patient the maxillary basal bone widths and interdental widths at the maxillary first molars and first and second premolars were measured on axial and coronal sections of CBCT images. In addition, the presence of permanent tooth agenesis and the widths of maxillary incisors were recorded. RESULTS: Similar maxillary transverse dimensions, both skeletally and dentally, were found between the PDC and control groups. In the PDC group, the number of patients with permanent tooth agenesis was six times higher than in the control group. In addition, the maxillary lateral incisors on PDC-affected sides were smaller than those of control group (P < .05). CONCLUSIONS: The maxillary transverse dimension, both skeletally and dentally, had no effect on the occurrence of PDC. The higher prevalence of permanent tooth agenesis was found in the PDC group. Moreover, the mean mesiodistal width of maxillary lateral incisors in the PDC group was significantly smaller than in the control group (P < .05).

Study in vivo intraocular biocompatibility of in situ gelation hydrogels: poly(2-ethyl oxazoline)-block-poly(ε-caprolactone)-block-poly(2-ethyl oxazoline) copolymer, matrigel and pluronic F127.

The long term in vivo biocompatibility is an essential feature for the design and development of sustained drug release carriers. In the recent intraocular drug delivery studies, hydrogels were suggested as sustained release carriers. The biocompatibility test for these hydrogels, however, was commonly performed only through in vitro cell culture examination, which is insufficient before the clinical applications. We compared three thermosensitive hydrogels that have been suggested as the carriers for drugs by their gel-solution phase-change properties. A new block terpolymer (PEOz-PCL-PEOz, ECE) and two commercial products (Matrigel® and Pluronic F127) were studied. The results demonstrated that the ocular media remained translucent for ECE and Pluronic F127 in the first 2 weeks, but cataract formation for Matrigel occurred in 2 weeks and for Pluronic F127 in 1 month, while turbid media was observed for both Matrigel and Pluronic F127 in 2 months. The electrophysiology examinations showed significant neuroretinal toxicity of Matrigel and Pluronic F127 but good biocompatibility of ECE. The neuroretinal toxicity of Matrigel and Pluronic F127 and superior biocompatibility of ECE hydrogel suggests ECE as more appropriate biomaterial for use in research and potentially in intraocular application.

Extended release of bevacizumab by thermosensitive biodegradable and biocompatible hydrogel.

The antibody bevacizumab (Avastin) has been used clinically to treat intraocular neovascular diseases based on its antivascular endothelial growth factor (VEGF) character. The anti-VEGF strategy for retinal neovascular diseases is limited by the short half-life of bevacizumab and thus requires frequent injections. This Article reports the sustained release of bevacizumab from a biocompatible material that is composed of a triblock copolymer of poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone)-b-poly(2-ethyl-2-oxazoline) (PEOz-PCL-PEOz). The amphiphilic PEOz-PCL-PEOz triblock copolymer was synthesized in three steps. First, the PEOz was polymerized by methyl p-toluenesulfonate and 2-ethyl-2-oxazoline (EOz), and the living end was terminated by potassium hydroxide methanolic solution. Subsequently, the hydroxyl-PEOz was used as a macroinitiator for the ring-opening polymerization of ε-caprolactone using a Tin(II) octoate catalyst to synthesize the telechelic hydroxylated PEOz-PCL. Finally, the PEOz-PCL-PEOz triblock copolymer was obtained using the 1,6-hexamethylene diisocyanateas a coupling reagent. The PEOz-PCL-PEOz was chemically and molecularly characterized by GPC, (1)H NMR, and FTIR, and its aqueous solution (ECE hydrogel) showed a reversible sol (room temperature)-gel (physiological temperature) phase transition, which serves as an easy antibody-packing system with extended release. The biodegradability of ECE hydrogel was assessed by the porosity formation at different periods by scanning electron microscopy. The ECE hydrogel had no in vitro cytotoxicity on the human retinal pigment epithelial cell line by flow cytometry. The histomorphology and electrophysiology of the rabbit neuroretina were preserved after 2 months of intravitreal injection. In conclusion, the ECE hydrogel has a temperature-sensitive sol-gel phase transition and is effective in vitro. Its intraocular biocompatibility demonstrated its great potential to be widely used in biomedical applications for extended drug release.