The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation

Choi, Wungrak,Noh, Hyemi,Yeo, Areum,Jang, Hanmil,Ahn, Hyea Kyung,Song, Yeon Jung,Lee, Hyung Keun The Korean Ophthalmological Society 2016 Korean Journal of Ophthalmology Vol.30 No.4

<P><B>Purpose</B></P><P>Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A was determined using an experimental murine dry eye model.</P><P><B>Methods</B></P><P>The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered twice per day to dry eye induced murine corneas for 1 week.</P><P><B>Results</B></P><P>The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL.</P><P><B>Conclusions</B></P><P>HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.</P>

Gr-1^intCD11b⁺ myeloid-derived suppressor cells accumulate in corneal allograft and improve corneal allograft survival

Choi, Wungrak,Ji, Yong Woo,Ham, Hwa-Yong,Yeo, Areum,Noh, Hyemi,Jin, Su-Eon,Song, Jong Suk,Kim, Hyeon Chang,Kim, Eung Kwon,Lee, Hyung Keun Federation of American Societies for Experimental 2016 Journal of Leukocyte Biology Vol.100 No.6

<P>We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1.Gr-1(+)CD11b(+) cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1(+)CD11b(+) cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1(int)CD11b(+) cells, but not Gr-1(hi)CD11b(+) cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-beta, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-gamma plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1(int)CD11b(+) cells. Furthermore, adoptive transfer of Gr-1(int)CD11b(+) cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-gamma in allograft areas is essential for development of Gr-1(int)CD11b(+) MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.</P>

Chemokine decoy receptor D6 mimicking trap (D6MT) prevents allosensitization and immune rejection in murine corneal allograft model

Choi, Wungrak,Byun, Yu Jeong,Jung, Eunae,Noh, Hyemi,Hajrasouliha, Amir R.,Sadrai, Zahra,Chang, Eunju,Lee, Joon H.,Lee, Hyung Keun Federation of American Societies for Experimental 2015 Journal of Leukocyte Biology Vol.97 No.2

<P>Epithelial D6 expression levels inversely correlate with corneal allograft rejection and generating D6 mimicking peptide, and decoy the inflammatory chemokines to facilitate graft survival.</P><P>Although corneal allotransplantation is performed in the immune-privileged cornea, many grafts are still rejected after transplantation. This study examined the role of chemokine receptor D6 expression in a corneal allograft rejection, investigated the modulation of D6 expression in cells, and determined the effect of D6 on graft survival. Interestingly, D6 was highly expressed in CD45<B><SUP>−</SUP></B> cells and the corneal epithelium of accepted corneal allografts. From the mouse corneal allograft model, TGF-<I>β</I> was found to play a key role in D6 up-regulation, leading to reduced CCL2, CCL5, and CCL3. To modulate D6 chemokine binding, a D6MT was developed and showed effective chemokine trapping through SPR and FACS assays. By treating corneal allografts with D6MT, the allograft survival rate was improved, and (lymph) angiogenesis was reduced. Direct allosensitization and DC LN homing was drastically reduced in the mouse corneal allograft model. These findings suggest that TGF-<I>β</I> is a positive regulator of D6 expression, and it is a potential therapeutic target to enhance the survival of corneal allografts.</P>

Effect of Intraoperative Mitomycin C on the Surgical Outcomes of Ahmed Glaucoma Valve Implantation with Ciliary Sulcus Tube Placement

Na Eun Kim(Na Eun Kim),Sung Sik Kim(Sung Sik Kim),Jihei Sara Lee(Jihei Sara Lee ),Kwanghyun Lee(Kwanghyun Lee),Hyoung Won Bae(Hyoung Won Bae),Sang Yeop Lee(Sang Yeop Lee),Wungrak Choi(Wungrak Choi),Ch 대한안과학회 2023 Korean Journal of Ophthalmology Vol.37 No.3

Purpose: To evaluate the effect of intraoperative mitomycin C (MMC) on the surgical outcomes of ciliary sulcus (CS) Ahmed glaucoma valve (AGV) tube placement. Methods: A retrospective review of medical records of 54 consecutive patients who underwent AGV implantation with tube placed in CS was performed. Consecutive cases operated without the use of intraoperative MMC from 2017 to 2019 were compared with consecutive cases operated with MMC from 2019 to 2021. Surgical failure was defined as intraocular pressure (IOP) exceeding 21 mmHg in two consecutive visits after postoperative 3 months or ≤30% IOP reduction, IOP ≤5 mmHg in two consecutive visits, or loss of light perception. Kaplan-Meier survival analysis and log-rank test were performed to compare the surgical failure rates. Results: A total of 54 eyes of 54 patients were investigated. Mean follow-up period after AGV implantation was 1.4 ± 0.8 years. The MMC group showed significantly lower IOP during the 1st postoperative month (20.5 ± 8.6 mmHg vs. 15.8 ± 6.4 mmHg, p = 0.027), but the difference did not persist 6 months after the surgery (p = 0.805). The mean number of postoperative antiglaucoma medications was significantly lower in the MMC group in the 1st postoperative month (p = 0.047) but no difference was found at 6 months. No statistical difference was noted in the rates of postoperative complications. Kaplan- Meier survival analysis showed comparable survival rates between MMC group and no MMC group (p = 0.356). Conclusions: The intraoperative use of MMC significantly lowered IOP in the 1st postoperative month but did not increase 6 months success rates in patients receiving AGV tube placement in CS.

Effect of red ginseng on visual function and vision-related quality of life in patients with glaucoma

Kwanghyun Lee,Heon Yang,Joo Yeon Kim,Wungrak Choi,Gong Je Seong,Chan Yun Kim,Jun Mo Lee,Hyoung Won Bae 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.6

Background: Red ginseng has been found to improve ocular perfusion and dry eye syndrome in glaucomatouseyes; however, its effects on visual function and vision-related quality of life have not beeninvestigated. This study sought to evaluate the effects of red ginseng on visual function and visionrelatedquality of life in glaucoma patients using contrast sensitivity and a questionnaire. Methods: Participants were randomly assigned to two groups in this prospective, randomized, doubleblindstudy: in one group, red ginseng was taken first, followed by a placebo, and in the other, placebowas taken first, followed by red ginseng. We measured and compared changes in contrast sensitivityand vision-related quality of life between the two groups. Contrast sensitivity was measured usingOPTEC® 6500P, and vision-related quality of life was evaluated using the 25-item National Eye InstituteVisual Function Questionnaire. One-way and two-way repeated measure analyses of variance were usedfor the comparison. Relationships between respective changes in dry eye syndrome and contrastsensitivity were also analyzed. Results: Daytime contrast sensitivity and ocular pain improved after the administration of red ginseng. Nighttime contrast sensitivity was improved in early or moderate glaucoma. Improved contrast sensitivitywas not associated with improvement in dry eye syndrome. Conclusion: Red ginseng could improve contrast sensitivity and ocular pain in patients with glaucoma. The mechanism underlying improvement in contrast sensitivity appears to be associated with enhancedretinal perfusion or retinal ganglion cell function, but not dry eye syndrome.

The Korean Social Life, Health and Aging Project-Health Examination Cohort

Ju-Mi Lee,Won Joon Lee,Hyeon Chang Kim,Wungrak Choi,Jina Lee,Kiho Sung,Sang Hui Chu,Yeong-Ran Park,Yoosik Youm 한국역학회 2014 Epidemiology and Health Vol.36 No.-

The Korean Social Life, Health, and Aging Project (KSHAP) is a population-based longitudinal study of health determinants among elderly Koreans. The target population of the KSHAP are people aged 60 years or older and their spouses living in a rural community of Korea. A complete enumeration survey was conducted in the first wave of the KSHAP on 94.7% (814 of 860) of the target population between December 2011 and July 2012. The KSHAP-Health Examination (KSHAP-HE) cohort consists of 698 people who completed additional health examinations at a public health center (n=533) or at their home (n=165). Face-to-face questionnaires were used to interview participants on their demographics, social network characteristics, medical history, health behaviors, cognitive function, and depression symptoms. Health center examinations included anthropometric measures, body impedance analysis, resting blood pressure measurement, radial artery tonometry, bone densitometry, the timed up-and-go test, and fasting blood analysis. However, only anthropometric measures, blood pressure measurement, and non-fasting blood analysis were available for home health examinations. Collaboration is encouraged and access to the KSHAP baseline data will be available via the website of the Korean Social Science Data Archive (http://www.kossda.or.kr).