Young Hee Yoon

Bio: Young Hee Yoon is an academic researcher from University of Ulsan. The author has contributed to research in topics: Visual acuity & Vitrectomy. The author has an hindex of 35, co-authored 180 publications receiving 4905 citations. Previous affiliations of Young Hee Yoon include Asan Medical Center.

Changes in Choroidal Thickness in Relation to the Severity of Retinopathy and Macular Edema in Type 2 Diabetic Patients

Abstract: PURPOSE: To assess changes in choroidal thickness in type 2 diabetic patients with diabetic retinopathy (DR) and diabetic macular edema (DME) using enhanced-depth imaging spectral domain optical coherence tomography (EDI-OCT). METHODS: Among 235 eyes from 145 patients, 195 treatment-naive eyes were divided into no DR, mild/moderate nonproliferative DR (NPDR), severe NPDR, proliferative DR (PDR), and 40 eyes having a history of laser panretinal photocoagulation (PRP) were classified as PRP-treated DR. Eyes with no ocular treatment (195 eyes) were divided according to the presence of and to the subtypes of DME. Subfoveal choroidal thickness (SFChT) and parafoveal choroidal thickness (PFChT) at 1500 μm were measured using EDI-OCT. RESULTS: Mean age was 62.6 ± 12.4 years, and mean duration of DM was 15.1 ± 7.2 years. Mean SFChT in groups with no DR (40 eyes), mild/moderate NPDR (47 eyes), severe NPDR (72 eyes), PDR (36 eyes), and PRP-treated DR (40 eyes) was 262.3 ± 68.4 μm, 244.6 ± 77.0 μm, 291.1 ± 107.7 μm, 363.5 ± 74.9 μm, and 239.9 ± 57.4 μm, respectively. Mean SFChT was significantly greater in eyes with PDR than in those with no DR (P < 0.01), mild/moderate NPDR (P < 0.01), or severe NPDR (P < 0.05). Mean SFChT decreased significantly in PRP-treated DR compared with PDR (P < 0.01). Eyes with DME (67 eyes) had a thicker subfoveal choroid than eyes without DME (128 eyes; P < 0.05) and, compared with cystoid or diffuse types, SFChT was thickest in subretinal detachment (SRD)-type DME (P < 0.05). CONCLUSIONS: Choroidal thickness increased significantly as the severity worsened from mild/moderate/NPDR to PDR, and decreased in PRP-treated eyes. The subfoveal choroid was thicker in eyes with DME than in those without, and was thickest in eyes with SRD-type DME.

Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells.

Abstract: Purpose To characterize and investigate the mechanism of chloroquine (CQ) retinotoxicity in human retinal pigment epithelium-derived ARPE-19 cells. Methods Cultured ARPE-19 cells were exposed to 10 to 250 μM CQ, and cell death was quantified using a lactate dehydrogenase release assay. Autophagy was studied in ARPE-19 cells transfected with GFP-LC3. Lysosomes in living cells were stained and observed by live-cell confocal microscopy. Results After exposure to CQ, ARPE-19 cells developed cytosolic vacuoles within 1 hour and underwent cell lysis within 24 hours. The levels of LC3-II, beclin-1 and, p62, as well as the number GFP-LC3- and RPF-LC3-positive autophagic vacuoles (AVs), increased after CQ treatment, indicating that autophagy was activated. However, lysosomal staining revealed that almost all AVs were separate from lysosomes; thus, fusion between AVs and lysosomes was completely blocked. In addition, the levels of ubiquitinated proteins and GFP-mHttp aggregates in ARPE-19 cells were increased by CQ, providing further evidence that autophagic degradation was inhibited. Conclusions CQ induces vacuole formation and cell death in ARPE-19 cells. Initially, vacuoles developed from enlarged lysosomes, followed by the activation of upstream steps in the autophagy pathway and the formation of LC3-positive AVs. Because CQ blocked the fusion of AVs with lysosomes, autophagic protein degradation was inhibited, indicating that CQ-induced retinotoxicity may be caused by the accumulation of potentially toxic ubiquitinated proteins.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion.

Abstract: Macroautophagy/autophagy is a conserved transport pathway where targeted structures are sequestered by phagophores, which mature into autophagosomes, and then delivered into lysosomes for degradati...

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

Abstract: Background Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. Methods We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstru...

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Enhanced Depth Imaging Optical Coherence Tomography of the Choroid in Normal Eyes

Abstract: PURPOSE To measure macular choroidal thickness in normal eyes at different points using enhanced depth imaging (EDI) optical coherence tomography (OCT) and to evaluate the association of choroidal thickness and age. DESIGN Retrospective, observational case series. METHODS EDI OCT images were obtained in patients without significant retinal or choroidal pathologic features. The images were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. Seven sections were obtained within a 5 x 30-degree area centered at the fovea, with 100 scans averaged for each section. The choroid was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 500-microm intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate variations of choroidal thickness at each location and to correlate choroidal thickness and patient age. RESULTS The mean age of the 30 patients (54 eyes) was 50.4 years (range, 19 to 85 years), and 14 patients (46.7%) were female. The choroid was thickest underneath the fovea (mean, 287 microm; standard deviation, +/- 76 microm). Choroidal thickness decreased rapidly in the nasal direction and averaged 145 microm (+/- 57 microm) at 3 mm nasal to the fovea. Increasing age was correlated significantly with decreasing choroidal thickness at all points measured. Regression analysis suggested that the subfoveal choroidal thickness decreased by 15.6 microm for each decade of life. CONCLUSIONS Choroidal thickness seems to vary topographically within the posterior pole. The thickness of the choroid showed a negative correlation with age. The decrease in the thickness of the choroid may play a role in the pathophysiologic features of various age-related ocular conditions.