• Journal of Animal Reproduction and Biotechnology
• /
• v.37 no.4
• /
• pp.292-297
• /
• 2022

Direct injection of CRISPR/Cas9 into zygotes enables the production of genetically modified nonhuman primates (NHPs) essential for modeling specific human diseases, such as Usher syndrome, and for developing novel therapeutic strategies. Usher syndrome is a rare genetic disease that causes loss of hearing, retinal degeneration, and problems with balance, and is attributed to a mutation in MYO7A, a gene that encodes an uncommon myosin motor protein expressed in the inner ear and retinal photoreceptors. To produce an Usher syndrome type 1B (USH1B) rhesus macaque model, we disrupted the MYO7A gene in developing zygotes. Identification of appropriately edited MYO7A embryos for knockout embryo transfer requires sequence analysis of material recovered from a trophectoderm (TE) cell biopsy. However, the TE biopsy procedure is labor intensive and could adversely impact embryo development. Recent studies have reported using cell-free DNA (cfDNA) from embryo culture media to detect aneuploid embryos in human in vitro fertilization (IVF) clinics. The cfDNA is released from the embryo during cell division or cell death, suggesting that cfDNA may be a viable resource for sequence analysis. Moreover, cfDNA collection is not invasive to the embryo and does not require special tools or expertise. We hypothesized that selection of appropriate edited embryos could be performed by analyzing cfDNA for MYO7A editing in embryo culture medium, and that this method would be advantageous for the subsequent generation of genetically modified NHPs. The purpose of this experiment is to determine whether cfDNA can be used to identify the target gene mutation of CRISPR/Cas9 injected embryos. In this study, we were able to obtain and utilize cfDNA to confirm the mutagenesis of MYO7A, but the method will require further optimization to obtain better accuracy before it can replace the TE biopsy approach.

• Journal of Life Science
• /
• v.30 no.8
• /
• pp.722-730
• /
• 2020

As one of the most serious health risk factors, air pollution can no longer be ignored. Particulate matter (PM) is an important and harmful component of air pollution that originates from a variety of sources. Numerous recent studies have linked PM to a range of conditions including cancer, cardiovascular, respiratory, and skin disease. The eye, despite being directly exposed to air pollution, has been investigated in very few of these studies. In this review, we describe the evidence from in vitro and in vivo studies, as well as epidemiological investigations, that supports the association between exposure to PM and the development of ocular conditions such as surface and retinal disease and glaucoma. Based on the results of previous studies, we suggest that PM exposure can lead to oxidative stress, inflammation, autophagy, and, ultimately, ocular surface disease. Nevertheless, almost no studies focus on ocular surface damage from PM while some epidemiological and clinical studies report on the posterior of the eye. However, the underlying pathological mechanisms in the posterior following PM exposure have yet to be identified, and further studies are therefore warranted of the ocular surface as well as the posterior part of the eye.

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.6
• /
• pp.679-683
• /
• 2005

Cancer associated retinopathy (CAR) syndrome is a very rare ocular manifestation of paraneoplastic syndrome, and is characterized clinically by progressive visual impairment. Immune cross-reactivity between antigens in the cancerous tissue and antigens in the retina may play an important role in its pathogenesis, and most of cases are associated with lung carcinoma, particularly small cell lung cancer. The clinical triad of CAR is described as photosensitivity, ring scotomata, and an attenuated retinal arterial caliber. Here, we report a 61-year old male patient with CAR syndrome, who had small cell lung carcinoma in the stage of limited disease, with a brief review of the relevant literature.

• Clinical and Experimental Pediatrics
• /
• v.54 no.5
• /
• pp.219-223
• /
• 2011

McKusick-Kaufman syndrome (MKS) is an autosomal recessive multiple malformation syndrome characterized by hydrometrocolpos (HMC) and postaxial polydactyly (PAP). We report a case of a female child with MKS who was transferred to the neonatal intensive care unit of Seoul National University Children's Hospital on her 15th day of life for further evaluation and management of an abdominal cystic mass. She underwent abdominal sonography, magnetic resonance imaging, genitography and cystoscopy which confirmed HMC with a transverse vaginal septum. X-rays of the hand and foot showed bony fusion of the left third and fourth metacarpal bones, right fourth dysplastic metacarpal bone and phalanx, right PAP and hypoplastic left foot with left fourth and fifth dysplastic metatarsal bones. In addition, she had soft palate cleft, mild hydronephroses of both kidneys, hypoplastic right kidney with ectopic location and mild rotation, uterine didelphys with transverse vaginal septum and low-type imperforated anus. She was temporarily treated with ultrasound-guided transurethral aspiration of the HMC. Our patient with HMC and PAP was diagnosed with MKS because she has two typical abnormality of MKS and she has no definite complications of retinal disease, learning disability, obesity and renal failure that develop in Bardet-Biedl syndrome, but not in MKS until 33 months of age. Here, we describe a case of a Korean patient with MKS.

• Childhood Kidney Diseases
• /
• v.6 no.2
• /
• pp.266-271
• /
• 2002

There are several diseases characterized by neurologic abnormalities and renal disease. Joubert syndrome is one of them. Joubert syndrome Is a relatively rare autosomal recessive syndrome. The most significant and constant neurologic finding is hypoplasia of the cerebellar vermis. Joubert syndrome is associated with hypotonia, retinal dystrophy, abnormal eye movement, delayed development, abnormal respiratory pattern (neonatal episodic tachypnea or apnea) and nephronophthisis. We report a boy with Joubert syndrome associated with nephrocalcinosis and agenesis of the cerebellar vermis. This patient had also abnormal eye movement, hypotonia, abnormal respiratory pattern, delayed development and chronic renal failure.

• Korean Chemical Engineering Research
• /
• v.62 no.1
• /
• pp.118-124
• /
• 2024

A neural network is utilized for preprocessing of de-noizing in electrocardiogram signals, retinal images, seismic waves, etc. However, the de-noizing process could provoke increase of computational time and distortion of the original signals. In this study, we investigated a neural network architecture to analyze measurement data without additional de-noizing process. From the dynamical behaviors of DNA in aqueous solution, our neural network model aimed to predict the mole fraction of each DNA in the solution. By adding white noise to the dynamics data of DNA artificially, we investigated the effect of the noise to neural network's predictions. As a result, our model was able to predict the DNA mole fraction with an error of O(0.01) when signal-to-noise ratio was O(1). This work can be applied as a efficient artificial intelligence methodology for analyzing DNA related to genetic disease or cancer cells which would be sensitive to background measuring noise.

• Journal of Veterinary Clinics
• /
• v.41 no.3
• /
• pp.178-182
• /
• 2024

A 10-year-old spayed female Poodle was referred for blindness. On ophthalmic examination, loss of bilateral ocular pupil light reflex, visual loss, and right retinal detachment were confirmed at a local hospital. Magnetic resonance imaging (MRI) of the brain was performed to identify the optic nerve, optic chiasm, and brain disease. A sessile mass centered on the region of the optic chiasm was identified. The mass had iso- to hypointense on fluid-attenuated inversion recovery and T2-weighted images and mildly hypointense on T1-weighted images compared to the gray matter, with strong contrast enhancement. Peripheral edema was also identified. Computed tomography (CT) brain perfusion was performed to obtain additional hemodynamic information about the patient using a multislice CT. CT perfusion showed that the cerebral blood volume in the left temporal lobe region (13.4 ± 1.6 mL/100 g) was decreased relative to the contralateral region (19.9 ± 0.3 mL/100 g). The patient showed decreased appetite and consciousness one week after the CT scan with clinical symptoms worsened. The patient had seizure, tetraparesis, and loss of consciousness. It was euthanized one month later at the request of the owner. This report suggests that CT brain perfusion can provide additional hemodynamic information such as insufficient brain perfusion in sellar region tumor which can help assess potential complications and prognosis and plan treatment.

• Clinical and Experimental Pediatrics
• /
• v.53 no.2
• /
• pp.163-166
• /
• 2010

Purpose : Leigh syndrome is a typical type of mitochondrial disease. This study was conducted to analyze the types of ophthalmologic symptoms and results of funduscopy conducted in the ophthalmologic examination of patients with Leigh syndrome. Methods : Funduscopy was conducted on 24 subjects, who were chosen among those diagnosed as having mitochondrial respiratory chain complex defect and who were clinically suitable for the criteria of Leigh syndrome. Their clinical features, ophthalmologic symptoms, and ophthalmologic examination results were retrospectively analyzed. Results : Of the 24 patients with Leigh syndrome, 11 developed ophthalmologic symptoms and no abnormal finding was observed in 13. The most frequent abnormal finding was visual disturbance in 5 patients. Funduscopy revealed abnormal findings in 17 patients; retinal pigmentation was the most frequent abnormality and was seen in 9 patients. Conclusion : Funduscopy can be an important screening test to find ophthalmologic abnormalities among patients with mitochondrial disease (MD), including those patients whose ophthalmologic symptoms are inconspicuous. It is predicted that an improved screening test can be made in the future that will identify risk factors related to ophthalmologic symptoms.

• Journal of The Korean Ophthalmological Society
• /
• v.59 no.11
• /
• pp.1024-1029
• /
• 2018

Purpose: We examined aqueous humor levels of 25-hydroxyvitamin D (vitamin D) in patients with age-related macular degeneration to investigate possible relationships between aqueous humor vitamin D levels and clinical manifestations. Methods: Patients > 50 years of age, 52 eyes of 34 patients with age-related macular degeneration, and 23 eyes of 17 patients treated with cataract surgery without retinal disease, were examined for aqueous humor vitamin D levels and compared. The experimental group was divided into two groups according to the median value of aqueous humor vitamin D levels. We compared the clinical manifestations of macular degeneration in both groups and identified relationships between aqueous humor vitamin D levels and clinical features. Results: Vitamin D levels in the aqueous humor were significantly lower in the experimental group than in the control group (experimental, $10.03{\pm}10.1ng/mL$ vs. control group, $40.8{\pm}16.4ng/mL$; p < 0.001). Patients with high vitamin D levels in the macular degeneration group had a higher percentage of fibrovascular pigment epithelial detachments than those in the low grade group (high grade group, 65% vs. low grade group, 27%; p = 0.003). Multiple linear regression analysis showed a significant correlation between vitamin D levels and the total number of anti-vascular endothelial growth factor intravitreal injections within 6 months (standardize coefficient, ${\beta}=-0.336$). Conclusions: Patients with wet age-related macular degeneration had significantly lower vitamin D levels in the aqueous humor compared to control group subjects of similar ages. However, in patients with macular degeneration, low vitamin D levels were associated with a greater number of intravitreal injections, while higher levels of vitamin D may lead to more advanced forms of fibrovascular retinal pigment epithelium and related low vision. These relationships were not always constant, so further studies on the relationships between local vitamin D levels and ocular disorders are needed.

• Radiation Oncology Journal
• /
• v.8 no.2
• /
• pp.169-176
• /
• 1990

Radiotherapy result was analyzed in 23 children with retinoblastoma treated in Seoul National University Hospital from 1980 to 1987. Three ($17\%$) had bilateral tumor at diagnosis. Among 20 children with unilateral retinoblastoma 13 children got radiotherapy after enucleation, 2 were treated with radiotherapy alone, and 5 were delivered with radiotherapy after relapse. Of 15 non-recurrent unilateral tumors, there were 5 stage II children, 8 stage III, and 2 stage IV by staging system proposed by St. Jude Children's Research Hospital. Chemotherapy was combined when resection margin of the optic nerve was positive or when malignant cell was found in CSF. Of 12 children who completed radiotherapy, local or distant failure was not found but 2 cases of relapse at the contralateral retina were observed. Their 5 year survival rate was $82.2\%$. Another case of contralateral relapse was detected in children who was treated with radiotherapy alone. Thus overall frequency of the bilateral disease was $33\%$. Prognosis of recurrent tumors were so poor that no cases of CR was obtained and that 3 year survival rate was $20\%$. Two of 3 bilateral cases at diagnosis were in NED status. Complication were sunken orbit only. Result of radiotherapy was so good in early stage or small bulk tumor that treatment delay after diagnosis must not be allowed.