Joo Youn Oh’s research while affiliated with Seoul National University Hospital and other places

Background: Toll-like receptor (TLR) 2 is a primary sensor of injury, and regulatory T cells (Tregs) are crucial mediators of tissue homeostasis. In this study, we aimed to investigate whether TLR2 is necessary for Treg-mediated restoration of corneal homeostasis following injury. Methods: We evaluated inflammatory corneal neovascularization and the proportions of Tregs, along with pro-angiogenic, pro-inflammatory monocytes, using a suture-induced corneal angiogenesis model in mice that either lacked TLR2 or were subjected to temporary TLR2 inhibition. The roles of injury-induced Tregs in corneal angiogenesis were further verified in vivo through adoptive transfer and in vitro using cultures of vascular endothelial cells. Results: Inflammatory corneal neovascularization was significantly more pronounced in TLR2 knockout mice compared to wild-type mice, while no differences were observed in TLR4 knockout mice. Temporary TLR2 inhibition also exacerbated corneal neovascularization, whereas TLR4 inhibition did not. Mechanistically, corneal injury induced an increase in Tregs in wild-type mice, which was absent in TLR2 knockout mice. Conversely, pro-angiogenic, pro-inflammatory monocytes were elevated in TLR2 knockout mice. Adoptive transfer of injury-induced Tregs from wild-type to TLR2 knockout mice reduced corneal neovascularization and decreased the number of monocytes. Functional assays demonstrated that Tregs from TLR2 knockout mice exhibited lower cell proliferation and IL-10 secretion, but increased IFN-γ secretion compared to Tregs from wild-type mice. Furthermore, TLR2 knockout Tregs were less effective at inducing apoptosis and suppressing pro-inflammatory activation and tube formation of vascular endothelial cells than their wild-type counterparts. Conclusion: Our findings suggest an expanded role for TLR2 in promoting corneal angiogenic and immunologic homeostasis during injury by regulating Treg numbers and functions.

To investigate the changes in ocular biometry over time and their impact on intraocular lens (IOL) calculation in adult Korean patients with cataracts. Inclusion criteria were patients who underwent two consecutive ocular biometric measurements spaced more than one year apart using the IOLMaster 700 between November 2019 and February 2024 at a tertiary hospital in Seoul, Korea. Longitudinal changes in ocular biometry were evaluated. Predictive errors were compared among patients who underwent cataract surgery using the SRK/T, Kane, Barrett Universal II, Cook K6, EVO, Hill-RBF, Hoffer QST, and Pearl DGS formulas. A total of 448 eyes from 448 patients were included. Ocular biometry measured over an average interval of 23.4 months showed that with increasing age, axial length elongated (0.04 ± 0.10 mm, p < 0.001), and the magnitude of total corneal astigmatism increased (0.04 ± 0.39 D, p = 0.018). The mean absolute predictive errors of the final measurements were significantly smaller compared to the initial measurements in the Barrett Universal II, EVO, Kane, and Pearl DGS formulas (difference of -0.05 D, -0.05 D, -0.06 D, and − 0.05 D, respectively). In the subgroup of eyes with an axial length of 25 mm or longer, the final measurements showed even greater reduction in mean absolute predictive errors across multiple formulas, including Barrett Universal II, Cook K6, EVO, Hill-RBF, Hoffer QST, Kane, and Pearl DGS, with reductions of -0.11 D, -0.11 D, -0.10 D, -0.08 D, -0.10 D, -0.09 D and − 0.10 D, respectively. Axial length increases and corneal curvature changes with aging. IOLMaster 700 ocular biometry results measured closer to the date of surgery were more accurate in IOL power calculation than those measured more than one year earlier, with the greatest improvement observed in myopic eyes. Therefore, it is recommended to repeat IOLMaster 700 biometry before surgery if the previous measurements were taken more than a year ago.

Background This study aimed to investigate the self-reported dissatisfaction rates and associated risk factors among patients who underwent cataract surgery using different types of presbyopia-correcting intraocular lenses (IOLs). Methods This retrospective case–control study analyzed the medical records in 340 eyes from 211 cataract surgery patients with presbyopia-correcting IOLs. The analyzed IOL types included bifocal (ReSTOR®), trifocal (PanOptix®), and extended depth-of-focus (EDOF; Symfony®) IOLs. The rates of self-reported dissatisfaction related to vision or photic disturbances were compared between these IOLs. Various factors, including sex, age, preoperative visual acuity and refractive status, and biometric indices, were analyzed to identify potential risk factors for dissatisfaction. Results The overall dissatisfaction rate was 18.5% (63/340). Among the IOL types, Symfony®-implanted eyes had the highest rate of near-vision dissatisfaction, while PanOptix®-implanted eyes showed similar proportions of photic disturbances and near-vision discomfort. The major risk factor identified for overall dissatisfaction, regardless of IOL type, was preoperative myopia, which aligns with the risk factor for near discomfort. Meanwhile, the risk factors for photic phenomena were revealed to be thinner corneal thickness and greater corneal astigmatism. By IOL types, preoperative myopia caused near-vision discomfort in Symfony® eyes, whereas greater corneal astigmatism and thinner corneas were linked to photic disturbances in PanOptix® eyes. Conclusions It suggests that near-vision discomfort is related to myopic factors, whereas photic disturbances are associated with ocular aberrations. The types of dissatisfaction vary depending on the designs of presbyopia-correcting IOLs. Trial Registration This retrospective study adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the Seoul National University Hospital on March 13, 2023 (IRB No: 2303–025-1409).

Background The purpose of the study was to evaluate the relationship between prediction errors (PEs) and ocular biometric variables in cataract surgery using nine intraocular lens (IOL) formulas with an explainable machine learning model. Methods We retrospectively analyzed the medical records of consecutive patients who underwent standard cataract surgery with a Tecnis 1-piece IOL (ZCB00) at a single center. We calculated predicted refraction using the following IOL formulas: Barrett Universal II (BUII), Cooke K6, EVO V2.0, Haigis, Hoffer QST, Holladay 1, Kane, SRK/T, and PEARL-DGS. We used a LightGBM-based machine learning model to evaluate the explanatory power of ocular biometric variables for PEs and assessed the relationship between PEs and ocular biometric variables using Shapley additive explanation (SHAP) values. Results We included 1,430 eyes of 1,430 patients in the analysis. The SRK/T formula exhibited the highest R² value (0.231) in the test set among the machine-learning models. In contrast, the Kane formula exhibited the lowest R² value (0.021) in the test set, indicating that the model could explain only 2.1% of the PEs using ocular biometric variables. BUII, Cooke K6, EVO V2.0, Haigis, Hoffer QST, Holladay 1, PEARL-DGS formulas exhibited R² values of 0.046, 0.025, 0.037, 0.194, 0.106, 0.191, and 0.058, respectively. Lower R² values for the IOL formulas corresponded to smaller SHAP values. Conclusion The explanatory power of currently used ocular biometric variables for PEs in new-generation formulas such as BUII, Cooke K6, EVO V2.0 and Kane is low, implying that these formulas are already optimized. Therefore, the introduction of new ocular biometric variables into IOL calculation formulas could potentially reduce PEs, enhancing the accuracy of surgical outcomes.

A 40-year-old woman visited our clinic for recurred pterygium and symblepharon in the right eye. She had a history of pterygium excision 8 years before. Over the course of 7 years, we performed pterygium excision combined initially with mitomycin C (MMC) application and conjunctival autograft. This was followed by three procedures using limbal allografts, MMC application, and amniotic membrane transplantation. All procedures were unsuccessful, resulting in aggressive recurrences of pterygial mass and symblepharon, extraocular movement limitation, corneal astigmatism, and decreased visual acuity. Ultimately, we applied a labial mucosal autograft after the recession of pterygial tissue. No complications were observed. Two and a half years postoperatively, the labial mucosal autograft was well-integrated into the conjunctival surface without symblepharon recurrence or abduction limitation. Corneal clarity was restored, and astigmatism was reduced, with no recurrence of pterygium. In conclusion, a labial mucosal autograft is a viable treatment option in complex cases of recalcitrantly recurrent pterygium with symblepharon.

Purpose To evaluate the agreement of ocular biometry measured using a swept-source optical coherence (Casia 2) and a dual Scheimpflug (Galilei G6) tomography in keratoconus. Methods This retrospective study included 102 eyes from 102 keratoconus patient examined using both devices. Parameters compared included flat (Kf) and steep (Ks) keratometry, astigmatism of anterior, posterior, and total keratometry, central (CCT) and thinnest (TCT) corneal thickness. To assess the agreement, intraclass coefficient (ICC) and Bland-Altman analysis with 95% limits of agreement (LoA) were used. Results Anterior and total Ks and Kf showed moderate or good agreement with 95% limits of agreement (LoA) range over 9.75 D. Posterior Ks and Kf were lower in the Galilei G6 (all p < 0.001). Astigmatism showed moderate, poor, and moderate agreement for anterior, posterior, and total keratometry, respectively. CCT and TCT showed excellent agreement; however, the 95% LoA range was over 60 μm. Conclusion The agreement between the two devices was not excellent for most parameters used to diagnose keratoconus and assess disease progression, and the differences were clinically significant. Therefore, the measurements from these two devices are not interchangeable for patients with keratoconus.

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been recognized as promising cytotherapeutics due to their demonstrated immunomodulatory effects in various preclinical models. The immunomodulatory capabilities of EVs stem from the proteins and genetic materials they carry from parent cells, but the cargo contents of EVs are significantly influenced by MSC tissues and donors, cellular age and culture conditions, resulting in functional variations. However, there are no surrogate assays available to validate the immunomodulatory potency of MSC‐EVs before in vivo administration. In previous work, we discovered that microcarrier culture conditions enhance the immunomodulatory function of MSC‐EVs, as well as the levels of immunosuppressive molecules such as TGF‐β1 and let‐7b in MSC‐EVs. Building on these findings, we investigated whether TGF‐β1 levels in MSC‐EVs could serve as a surrogate biomarker for predicting their potency in vivo. Our studies revealed a strong correlation between TGF‐β1 and let‐7b levels in MSC‐EVs, as well as their capacity to suppress IFN‐γ secretion in stimulated splenocytes, establishing biopotency and surrogate assays for MSC‐EVs. Subsequently, we validated MSC‐EVs generated from monolayer cultures (ML‐EVs) or microcarrier cultures (MC‐EVs) using murine models of experimental autoimmune uveoretinitis (EAU) and additional in vitro assays reflecting the Mode of Action of MSC‐EVs in vivo. Our findings demonstrated that MC‐EVs carrying high levels of TGF‐β1 exhibited greater efficacy than ML‐EVs in halting disease progression in mice with EAU as well as inducing apoptosis and inhibiting the chemotaxis of retina‐reactive T cells. Additionally, MSC‐EVs suppressed the MAPK/ERK pathway in activated T cells, with treatment using TGF‐β1 or let‐7b showing similar effects on the MAPK/ERK pathway. Collectively, our data suggest that MSC‐EVs directly inhibit the infiltration of retina‐reactive T cells toward the eyes, thereby halting the disease progression in EAU mice, and their immunomodulatory potency in vivo can be predicted by their TGF‐β1 levels.

Background: Mesenchymal stem/stromal cells (MSCs) maintain tissue homeostasis in response to microenvironmental perturbations. Toll-like receptors (TLRs) are key sensors for exogenous and endogenous signals produced during injury. In this study, we aimed to investigate whether TLRs affect the homeostatic functions of MSCs after injury. Methods: We examined the expression of TLR2, TLR3 and TLR4 in MSCs, and analyzed the functional significance of TLR2 activation using single-cell RNA sequencing. Additionally, we investigated the effects and mechanisms of TLR2 and its downstream activation in MSCs on the MSCs themselves, on monocytes/macrophages, and in a mouse model of sterile injury-induced inflammatory corneal angiogenesis. Results: MSCs expressed TLR2, which was upregulated by monocytes/macrophages. Activation of TLR2 in MSCs promoted their immunoregulatory and angiostatic functions in monocytes/macrophages and in mice with inflammatory corneal angiogenesis, whereas TLR2 inhibition attenuated these functions. Single-cell RNA sequencing revealed AKR1C1, a gene encoding aldo-keto reductase family 1 member C1, as the most significantly inducible gene in MSCs upon TLR2 stimulation, though its stimulation did not affect cell compositions. AKR1C1 protected MSCs against ferroptosis, increased secretion of anti-inflammatory cytokines, and enhanced their ability to drive monocytes/macrophages towards immunoregulatory phenotypes, leading to the amelioration of inflammatory corneal neovascularization in mice. Conclusion: Our findings suggest that activation of TLR2-AKR1C1 signaling in MSCs serves as an important pathway for the survival and homeostatic activities of MSCs during injury.

Purpose This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b⁺ cells in a mouse model of suture-induced corneal neovascularization. Methods Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2⁺CD11b⁺ cells and VEGFR-3⁺CD11b⁺ cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry. Results Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3⁺CD11b⁺ cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2⁺CD11b⁺ cells was unaffected. Conclusion Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3⁺CD11b⁺ cells.