Development of an Instrument for Slit-lamp Examination of Donor Corneas in Preservation Medium

Purpose@#To evaluate the effectiveness of an instrument devised for slit-lamp examination of donor corneas suspended in preservation medium. @*Methods@#The study examined two donor corneas received at Yeouido St. Mary's Hospital in February 2023 and March 2023. The instrument has three main components: a plastic holder to hold the preservation medium bottle, a cube with a mirror for reflecting the slit beam, and a stand to attach the device to the slit-lamp. Using the instrument, the donor corneas were examined via slit-lamp: microscopy with the endothelium facing upward and downward. Specular microscopy and anterior segment optical coherence tomography (OCT) were also performed on the preserved donor corneas. @*Results@#Slit-lamp examination of donor corneas in preservation medium using the instrument showed overall corneal buttoning and optical sections of the donor cornea. Using specular reflection and retroillumination, the endothelial layer was partially visible. However, specular microscopy and anterior segment OCT could not examine the donor cornea in preservation medium using the instrument. @*Conclusions@#The devised instrument facilitates slit-lamp examination of donor corneas in preservation medium, enabling a qualitative assessment of donor corneas before corneal transplantation surgery.

The Diagnosis and Treatment of a Post-traumatic Iris Cyst Referred as an Iris Tumor

Purpose@#We report the diagnosis and treatment of a secondary iris cyst in a patient referred for an iris tumor.Case summary: A 29-year-old man diagnosed with an anterior chamber mass of the left eye was referred to our center for further evaluation and management. Twenty years previously, he suffered a penetrating ocular injury of his left eye and underwent primary closure. He had no underlying systemic disease. At his initial visit, the best corrected visual acuity of his left eye was 0.5. A whitish-gray mass was observed within the anterior chamber from 1 o'clock to 5 o'clock, obscuring the pupil. Anterior segment optical coherence tomography revealed a cystic mass touching the retrocorneal surface. No other lesions were seen on orbital imaging or ocular ultrasonography. Ultimately, it was diagnosed as an iris cyst that occurred secondary to ocular trauma. After needle aspiration and intracystic injection of 99% ethanol, the cyst collapsed fully. However, a cataract developed within a few months, and phacoemulsification and intraocular lens implantation were performed. Seven months after cyst aspiration, the uncorrected visual acuity of the left eye had recovered to 0.5. The cyst still adhered to the corneal endothelium, remaining in its collapsed state. The current corneal endothelial cell density is 871 cells/mm2. @*Conclusions@#A secondary iris cyst was diagnosed in a patient with a history of penetrating eye trauma and surgery. It was treated successfully with needle aspiration and intracystic alcohol injection.

Ten-year Trends in Infectious Keratitis in South Korea

Purpose@#This study investigated the causative microorganisms, antibiotic susceptibility, and risk factors of infectious keratitis over the past 10 years. @*Methods@#Data from patients with infectious keratitis who underwent microbial culture tests from 2012 to 2021, obtained from anonymized data systems, were analyzed. Microbial culture results and antibiotic susceptibility profiles were examined. A retrospective analysis of the medical records of patients with infectious keratitis during the same period was conducted to investigate the clinical characteristics and risk factors. @*Results@#Data from 1,837 cases of infectious keratitis were extracted from anonymized records. The culture positive rate among patients was 46.0% (1,137/2,474), with coagulase-negative Staphylococcus (CoNS) being the most common causative organism (27.8%). Increased resistance to cefazolin and cefotaxime was observed in gram-negative bacteria, while there were no significant temporal changes in quinolone resistance in gram-positive or negative bacteria. A retrospective medical record analysis of 288 cases revealed that older patients, as well as those with an initial corrected visual acuity < 0.1, a history of ocular surgery, pre-existing ocular conditions, prior steroid eye drops, or glaucoma eye drops, had significantly higher rates of culture positivity. Multivariate analysis identified risk factors for severe keratitis requiring surgical intervention as a symptom-to-presentation period of 7 days or longer (p = 0.048) and pre-existing ocular conditions (p = 0.040). @*Conclusions@#CoNS was the most common microorganism causing infectious keratitis over the past decade. There has been an increase in resistance to cephalosporin antibiotics among gram-negative bacteria. Patients with pre-existing ocular conditions may require surgical intervention, so infectious keratitis in these patients requires greater attention.

Categorization of Meibomian Gland Dysfunction Using Lipid Layer Thickness and Meibomian Gland Dropout in Dry Eye Patients: A Retrospective Study

Purpose@#In the present study, we determined the prevalence of obstructive meibomian gland dysfunction (MGD), hyposecretory MGD, grossly normal MG, and hypersecretory MGD in patients with dry eye syndrome using lipid layer thickness (LLT) and MG dropout. @*Methods@#Eighty-eight patients with dry eye syndrome were included in the study. Patients were categorized into four groups according to the LLT and weighted total meiboscore. The proportion of patients in each group was calculated. The age, sex, Ocular Surface Disease Index, LLT, Schirmer, tear film breakup time, cornea stain, weighted total meiboscore, expressibility, and quality of meibum were compared between the four groups. @*Results@#Fifteen eyes (17.0%) had obstructive MGD, two eyes (2.3%) had hyposecretory MGD, 40 eyes (45.5%) had grossly normal MG, and 17 eyes (19.3%) had hypersecretory MGD. The obstructive MGD group was younger than the grossly normal MG group. In obstructive MGD, the ratio of men to women was higher than that of the other groups. However, Ocular Surface Disease Index, Schirmer, tear film breakup time, and corneal stain did not show statistically significant differences between the four groups. The meibum expressibility of the hyposecretoy MGD group was worse than those of the other groups. The meibum expressibility of the hyposecretoy MGD group was poor than those of the obstructive and hypersecretory MGD group. @*Conclusions@#This categorization was expected to help determine the best treatment method for dry eye syndrome, according to the MG status.

In Vivo Human Lacrimal Gland Imaging Using an Ultrasound Biomicroscopy

Purpose@#In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings @*Methods@#The representative UBM findings of palpebral lobes in seven subjects (four with non-Sjögren dry eye syndrome, one with Sjögren syndrome, and two healthy subjects) were described in this study. To prolapse the palpebral lobe, the examiner pulled the temporal part of the upper eyelid in the superotemporal direction and directed the subject to look in the inferonasal direction. We scanned the palpebral lobes longitudinally and transversely using UBM. We used an Aviso UBM with a 50 MHz linear probe and ClearScan. @*Results@#In UBM of two healthy subjects, the echogenicity of the lacrimal gland was lower than that of the sclera and homogeneous. But the parenchyma of a patient with Sjögren dry eye syndrome was quite inhomogeneous compared to the healthy subjects. In two patients with dry eye syndrome, we were able to observe some lobules in the parenchyma. We could find excretory ducts running parallel at the surface of the longitudinal section in some subjects. In the longitudinal UBM scan of a subject, we observed a tubular structure at a depth of 1,500 μm that was considered a blood vessel. It ran from the superonasal to the inferotemporal direction. In a subject, we observed a large cyst beneath the conjunctiva. @*Conclusions@#Lacrimal gland imaging using UBM has both advantages of optical coherence tomography and sonography, and could be useful for evaluating dry eye syndrome.

Trends in Corneal Transplantation Revealed by KONOS and Health Insurance Review and Assessment Service Annual Reports

Purpose@#To analyze trends in corneal transplantation surgery and determine the number of domestic and imported corneal grafts used in South Korea.Method: The total number of keratoplasties and number of each individual surgical procedure conducted in 2010 and 2020 were identified using Health Insurance Review and Assessment Service data. The number of keratoplasties using domestic corneas in 2010 and 2020 was determined from the annual report of the Korean Network for Organ Sharing (KONOS). The number of keratoplasties using imported corneas was calculated by subtracting the number of keratoplasties using domestic corneas from the total number of keratoplasties. @*Results@#In 2010, 802 keratoplasties were performed in Korea, of which 299 (37.3%) used imported corneas; 715 (89.2%) were penetrating keratoplasties and 87 (10.8%) were anterior lamellar keratoplasties. In 2020, 911 keratoplasties were done in Korea and 564 (61.9%) used imported corneas; 541 (59.4%) were penetrating keratoplasties, 60 (6.6%) were anterior lamellar keratoplasties, and 310 (34.0%) were endothelial keratoplasties. From 2010 to 2020, the number of penetrating keratoplasties in Korea decreased, while the numbers of endothelial keratoplasties and keratoplasties using imported corneas increased. @*Conclusions@#There was a 30% decrease in the number of penetrating keratoplasties from 2010 to 2020, and a 30% increase in the numbers of endothelial keratoplasties and keratoplasties using imported corneas. The proportions of endothelial keratoplasties and imported corneas have increased steadily in Korea over the last 10 years.

Professional self-concept, self-leadership, job stress and fatigue on clinical competence of dental hygienists / 대한구강보건학회지

Objectives@#This study examines the relationship of dental hygienists’ professional self-concept, self-leadership, job stress, and fatigue with their clinical competence in order to identify factors that can improve clinical competence. This study is intended to provide basic information to develop educational programs for dental hygienist’s clinical competence. @*Methods@#The self-administered questionnaire survey was conducted with 243 dental hygienists working at dental clinics in Gwangju and Jeonnam from August 14, 2017 to September 9, 2017.The data regarding the general characteristics, professional self-concept, self-leadership, job stress and fatigue, and clinical competence were collected, and analyzed through independent t-tests, one-way analysis of variance (ANOVA), Pearson’s correlation coefficient, and multiple regression analysis using the SPSS Windows ver. 22.0. @*Results@#High professional self-concept (r=0.54) and self-leadership(r=0.48) were associated with high clinical competence. High self-leadership (r=0.53) was associated with high professional selfconcept. High fatigue(r=―0.21) was associated with low professional self-concept(P<0.01). The highest factor influencing clinical competence was professional self-concept, followed by selfleadership, total clinical experience, education level, and fatigue (P<0.05). @*Conclusions@#Based on the findings, it is necessary to develop educational programs which can improve autonomy and develop professionalism to enhance clinical competence in consideration of work experience and educational levels in dental hygienists.

Novel Method Measuring Conjunctival Microvascular Blood Flow Velocity by Zoom-lens, Ultra-high-speed Camera Attached Slit-lamp Biomicroscope

Purpose@#To introduce an intuitive method for measuring conjunctival microvascular blood flow velocity by imaging bulbar conjunctival microvessels using a slit-lamp biomicroscope equipped with a zoom lens and an ultra-high-speed camera. @*Methods@#After obtaining consent from 10 patients (1 male, 9 females) who visited Yeouido St. Mary’s Hospital from August 21, 2020, to June 12, 2021, the patients were examined under a slit lamp microscope equipped with an ultra-high-speed camera and zoom lens. The blood flow in the conjunctival microvessels was photographed. The captured images were analyzed with ImageJ software to measure the blood flow velocity in the conjunctival microvessels, and we investigated whether the blood flow velocity correlated with the vessel diameter and age. @*Results@#The median age of the subjects was 49.0 years. The mean conjunctival blood flow velocity in 53 microvessels was 0.786 ± 0.468 mm/s. The median conjunctival microvascular diameter was 7.06 μm (interquartile range 5.84 to 9.23 μm). The conjunctival microvascular diameter and blood flow velocity were not significantly correlated (Spearman’s p = 0.177), and the subjects’ age and conjunctival microvascular blood flow velocity were also not correlated (Spearman’s p = 0.669). @*Conclusions@#In this study, the blood flow velocity in the bulbar conjunctival microvessels could be measured easily by means of image analysis using a slit-lamp microscope equipped with an ultra-high-speed camera with a zoom lens.

Comparison of Anterior Segment Measurements Between Swept-source Optical Coherence Tomography and Schiempflug Coherence Interferometer

Purpose@#To assess the agreement between anterior segment measurements obtained using swept-source optical coherence tomography (Anterion®, Heidelberg Engineering Inc., Heidelberg, Germany) and Scheimpflug partial coherence interferometry (Pentacam HR®, OCULUS, Wetzlar, Germany). @*Methods@#We analyzed the anterior and posterior corneal keratometry, Cartesian astigmatism (J0), oblique astigmatism (J45), anterior chamber depth (ACD), and central corneal thickness (CCT) measurements obtained using the two devices in 65 eyes of 43 subjects. @*Results@#The mean differences between the anterior flat K, anterior steep K, anterior mean K, anterior J0, anterior J45, posterior flat K, posterior steep K, posterior mean K, posterior J0, posterior J45, ACD, and CCT measurements were -0.13 ± 0.34, -0.02 ± 0.33, -0.05 ± 0.31, -0.03 ± 0.39, -0.06 ± 0.35, 0.12 ± 0.09, 0.07 ± 0.08, 0.10 ± 0.06, -0.02 ± 0.14, 0.01 ± 0.16, 0.04 ± 0.06, and -3.51 ± 7.42, respectively. All measurements except posterior J0 and J45 had interclass correlation coefficients greater than 0.75. @*Conclusions@#The mean differences and 95% limits of agreement in this study are consistent with previously reported values. There was a high level of agreement between Anterion® and Pentacam HR®. However, considering the statistically significant differences and limits of agreement for certain measurements, caution should be exercised when assuming interchangeability between these devices.

Risk Factors Associated with Medication Adherence in HIV/AIDS Patients

Background@#Adherence to antiretroviral treatment (ART) is crucial for maintaining the HIV-RNA suppression in patients living with HIV/AIDS. This study aims to analyze the risk factors contributing to low medication adherence among individuals with HIV/ AIDS by analyzing data from the Korean HIV/AIDS cohort study. @*Methods@#The dependent variable is ART medication adherence.The depressive symptom and anxiety scores were collected as main independence variables. Covariates included gender, age, transmission route, alcohol and smoking information, and antiviral treatment regimen details. To predict the relationship between ordinal dependent variables and independent variables, an ordered logistic regression analysis was conducted, and odds ratios (OR) were calculated. @*Results@#The results of the ordered logistic regression analysis showed that female was associated with a higher risk of low medication adherence (OR=2.91, 95% CI=1.08, 7.83). Among the subjects who were non-smokers and non-drinkers, the risk of low medication adherence was lower (OR=0.36, 95% CI=0.18, 0.70). Depending on the ART treatment group, individuals taking integrase inhibitor had a lower risk of medication adherence (OR=0.31, 95% CI=0.13, 0.76), and those experiencing depressive symptoms were related with a higher risk of low medication adherence (OR=1.97, 95% CI=1.12, 3.46). @*Conclusions@# The encouragement and emotional support of healthcare professionals are essential for patients living with HIV/AIDS who experience depressive symptoms to maintain ART adherence. Additionally, further research is needed to ensure that HIV/AIDS infected female with concurrent depressive symptoms can achieve appropriate ART therapeutic effect.

Comparison of Meibomian Gland Loss between Demodex-infested Group and Dry Eye Patients without Demodex Infestation

Purpose@#To compare the degree of meibomian gland drop-out associated with Demodex infestation using non-contact meibography. @*Methods@#We performed noncontact meibography using an infrared digital camera on 24 adult subjects infested by Demodex and 40 without infestation. The right upper and lower lids were scored based on the loss of meibomian glands, and the scores of the upper and lower eyelids were summed to obtain the total meiboscore for each subject. Meiboscores were evaluated according to Demodex infestation and gender in each group. @*Results@#Sixty-four eyes of 64 people were enrolled in this study. The study subjects had an average age of 67.9 years (range, 40-79 years; men, 65.2 years; women, 69.1 years). There was a significant association between Demodex infestation and total meiboscore and upper and lower eyelid meiboscores (p = 0.000, p = 0.002, p = 0.004, respectively). There was no significant difference in the meiboscores between men and women. Age and meiboscore suggested a weak positive correlation; however, the R2 value was low, due to the concentrated age distribution of the study population. @*Conclusions@#Based on noncontact meibography, the authors concluded that the prevalence of changes in the meibomian glands was significantly related to Demodex infestation; however, there was no significant difference between men and women.

Comparison of the Effects of Orthokeratology Lens and Cyclopentolate on Myopia Progression in Children

Purpose@#To compare the effects of orthokeratology lens (Ortho‐K lens) and topical cyclopentolate on myopia progression in children. @*Methods@#This retrospective study analyzed the medical records of 36 children who received Ortho‐K lens and 28 who received cyclopentolate (i.e., total of 64 eyes). The following data were recorded: sex, age, age at first intervention, follow‐up duration, and visual acuity and axial length (AL) at the time of first treatment and after 6, 12, and 24 months of treatment. @*Results@#In the Ortho‐K group, the changes of AL significantly decreased by 0.3 ± 0.25 mm at 12 months and 0.52 ± 0.34 mm at 24 months (p for trend < 0.001). In the cyclopentolate group, the changes of AL significantly decreased by 0.36 ± 0.17 mm at 12 months and 0.62 ± 0.29 mm at 24 months (p for trend = 0.022). Compared to the use of cyclopentolate, the use of Ortho‐K lens resulted in smaller changes in AL during follow‐up (p = 0.038). @*Conclusions@#In myopic children, Ortho‐K reduced myopia progression, whereas cyclopentolate significantly less affect myopia progression than Ortho‐K lens.

Combined Mesenchymal Stem Cells and Cartilage Acellular Matrix Injection Therapy for Osteoarthritis in Goats

Background@#Human umbilical cord blood-derived MSCs (hUCB-MSCs) have been studied in osteoarthritis (OA) and cartilage regeneration. Our previous study demonstrated that hUCB-MSCs combined with cartilage acellular matrix injection (CAM Inj.) represent potential therapeutic agents for structural improvement and anti-inflammatory effects in a rabbit model of OA. @*Methods@#Based on a previous study, this study has evaluated the safety and efficacy of hUCB-MSCs combined with CAM Inj. in an anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx) in a goat model. In this study, 27 goats were divided into 5 groups: normal (n = 3), OA (n = 6), OA + CAM Inj. (n = 6), OA + hUCB-MSCs (n = 6), and OA + hUCB-MSCs + CAM Inj. (n = 6). Lameness and radiographic parameters were assessed 6 months after administration, and macroscopic and histological evaluations of the goat articular cartilage were performed 6 months after intervention. @*Results@#The results showed significant improvement in lameness score only in the OA + hUCB-MSCs group at 5 months after treatment (*p < 0.05), whereas the K&L score showed significant improvement only in the OA + hUCB-MSCs + CAM Inj. group 6 months after intervention (*p< 0.05). In addition, the gross findings showed significance in OA + CAM Inj. and OA + hUCB-MSCs + CAM Inj. groups 6 months after treatment (*,p < 0.05 and **p < 0.01). @*Conclusion@#In conclusion, treatment with a combination of hUCB-MSCs and CAM Inj. reduced OA symptoms and induced effective cartilage tissue repair in a goat model. We suggest the combination of hUCB-MSCs and CAM Inj. as an alternative therapy for OA.

Immunomodulatory Effect of Epidermal Growth Factor Secreted by Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells on Atopic Dermatitis

Background and Objectives@#Human mesenchymal stem cells (MSCs) are emerging as a treatment for atopic dermatitis (AD), a chronic inflammatory skin disorder that affects a large number of people across the world. Treatment of AD using human umbilical cord blood-derived MSCs (hUCB-MSCs) has recently been studied. However, the mechanism underlying their effect needs to be studied continuously. Thus, the objective of this study was to investigate the immunomodulatory effect of epidermal growth factor (EGF) secreted by hUCB-MSCs on AD. @*Methods@#and Results: To explore the mechanism involved in the therapeutic effect of MSCs for AD, a secretome array was performed using culture medium of hUCB-MSCs. Among the list of genes common for epithelium development and skin diseases, we focused on the function of EGF. To elucidate the effect of EGF secreted by hUCB-MSCs, EGF was downregulated in hUCB-MSCs using EGF-targeting small interfering RNA. These cells were then co-cultured with keratinocytes, Th2 cells, and mast cells. Depletion of EGF disrupted immunomodulatory effects of hUCB-MSCs on these AD-related inflammatory cells. In a Dermatophagoides farinae-induced AD mouse model, subcutaneous injection of hUCB-MSCs ameliorated gross scoring, histopathologic damage, and mast cell infiltration. It also significantly reduced levels of inflammatory cytokines including interleukin (IL)-4, tumor necrosis factor (TNF)-α, thymus and activation-regulated chemokine (TARC), and IL-22, as well as IgE levels. These therapeutic effects were significantly attenuated at all evaluation points in mice injected with EGF-depleted hUCB-MSCs. @*Conclusions@#EGF secreted by hUCB-MSCs can improve AD by regulating inflammatory responses of keratinocytes, Th2 cells, and mast cells.

Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid

Background and Objectives@#Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. @*Methods@#and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. @*Conclusions@#We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

Descemet Membrane Endothelial Keratoplasty after Penetrating Keratoplasty Graft Failure

Purpose@#To report a case of a successful secondary Descemet membrane endothelial keratoplasty in failed penetrating keratoplasty. Case summary: A 46-year-old male with keratoconus in both of his eyes underwent penetrating keratoplasty in his right eye 30 years ago and in his left eye 14 years ago. From one and a half year ago, the patient’s visual acuity decreased in his left eye due to graft failure. For treatment, secondary Descemet membrane endothelial keratoplasty was performed. Partial detachment of Descemet membrane was observed at 13 days after the operation, and an additional air injection was performed. At 8 months after the operation, the patient’s uncorrected visual acuity improved to 0.5 and the cornea maintained its clearance without rejection. @*Conclusions@#Secondary Descemet membrane endothelial keratoplasty was successfully performed in a patient with failed penetrating keratoplasty.

Descemet Stripping Automated Endothelial Keratoplasty for Repeated Penetrating Keratoplasty Graft Failure

Purpose@#To report a case of Descemet stripping automated endothelial keratoplasty (DSAEK) for graft failure after re-penetrating keratoplasty (PK).Case summary: A 33-year-old man of Indian nationality who had developed right eye amoeba keratitis and had received two penetrating keratoplasties and allogeneic kerato-limbal transplant in India sought treatment at our hospital. During the follow-up, Ahmed valve transplantation was performed under the diagnosis of secondary glaucoma in his right eye; the patient also underwent conjunctival recession and conjunctival permanent amniotic membrane transplantation as corneal neovascularization had progressed. Subsequently, the corneal transplantation failed and DSAEK was performed. At 7 months after the operation, the right-eye visual acuity was 20/320 without any complications. @*Conclusions@#DSAEK may restore good vision without complications in patients with repeated corneal graft failure after PK from corneal endothelial cell failure followed by corneal neovascularization and glaucoma surgery but with good stromal conditions. We present this case, along with a review of the literature. Future studies will require more surgical patients.

Repeat Descemet Membrane Endothelial Keratoplasty after Descemet Membrane Endothelial Keratoplasty Graft Failure

Purpose@#To report a case of secondary Descemet membrane endothelial keratoplasty (DMEK) for graft failure after primary DMEK.Case summary: A 47-year-old female underwent primary DMEK in her left eye with a diagnosis of Fuchs’ endothelial dystrophy. At 6 weeks later, corneal stromal edema with epithelial and subepithelial bullae was first observed. From that point on, the condition of the cornea and the visual acuity continued to degrade. After 7 months, a second DMEK procedure (i.e., a repeat DMEK) for graft failure was performed successfully without any complications. Since the second procedure, the cornea has been clear, and the best-corrected visual acuity has remained at 0.6 for 8 months. @*Conclusions@#To manage graft failure after primary DMEK, we performed a second DMEK procedure. The removal of the previous graft was easy, and there were no complications. Thus, repeat DMEK may be a feasible procedure.

Association with Corneal Remodeling Related Genes, ALDH3A1, LOX, and SPARC Genes Variations in Korean Keratoconus Patients

Purpose@#To determine whether the cornea remodeling-related genes aldehyde dehydrogenase 3A1 (ALDH3A1), lysyl oxidase (LOX), and secreted protein acidic and rich in cysteine (SPARC) were potential susceptibility candidate genes for keratoconus in Korean patients, we investigated the associations of single nucleotide polymorphisms (SNPs) in these three genes in Korean patients with keratoconus. @*Methods@#Genomic DNA was extracted from blood samples of unrelated patients with keratoconus and healthy control individuals. For screening of genetic variations, all exons from the entire coding regions of the ALDH3A1, LOX, and SPARC genes were directly sequenced to determine the presence of mutations. Control individuals were selected from the general population without keratoconus. @*Results@#In this study, we detected nine SNPs in ALDH3A1, four SNPs in LOX, and 18 SNPs in SPARC. rs116992290, IVS3-62c>t, rs116962241, and rs2228100 in ALDH3A1 and rs2956540 and rs1800449 in LOX were significantly different between patient and control groups. In the SPARC gene, the distribution of the *G allele of EX10+225 T>G (p = 0.018; odds ratio, 1.869) was strongly associated with the risk of keratoconus in the Korean population. In haplotype analysis, C-G of rs2956540-rs2288393 in LOX(p = 0.046) and C-C-G and G-G-G of rs60610024-rs2228100-rs57555435 (p = 0.021 and p g - rs116962241 in ALDH3A1(p = 0.048) predisposed significantly to keratoconus. After cross-validation consistency and permutation tests, two locus model was the best SNP variations interaction pattern. @*Conclusions@#Our results suggested that genetic variations in ALDH3A1, LOX, and SPARC genes were associated with a predisposition for keratoconus in Korean individuals. Moreover, variations in ALDH3A1 and LOX may serve as strong biomarkers for keratoconus.

Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice

Background@#Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. @*Objectives@#The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. @*Methods@#We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. @*Results@#Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. @*Conclusions@#iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.