• Korean Journal of Veterinary Research
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• v.58 no.4
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• pp.219-221
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• 2018

A 2-year-old intact female Bengal cat was presented with a 6-month history of visual impairment. The cat manifested bilateral negative menace responses and dazzle reflexes and sluggish pupillary light reflexes. Bilateral fundus changes included generalized tapetal hyperreflectivity, advanced retinal vascular attenuation, and increased pallor of the optic disc. A diagnosis of bilateral retinal degeneration was made. The clinical findings suggest that the investigated Bengal cat was most likely to have an inherited retinal degeneration. Further studies of the Bengal cat breed are needed to determine the prevalence of inherited retinal degeneration in this breed in Korea.

• Korean Journal of Veterinary Research
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• v.53 no.2
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• pp.137-141
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• 2013

To report retinal image of in a 6-year-old male castrated poodle dog with a 2-month history of nyctalopia using optical coherence tomography (OCT). Ocular reflexes were present in both eyes and slit lamp examination showed anterior subscapular cataract in the right eye. There were fundus abnormalities in both eyes similar to retinal degeneration. Scotopic electroretinograms (ERGs) revealed significantly subabnormal amplitudes and prolonged implicit time, whereas photopic ERGs were better maintained, although far from normal. OCT of affected dogs revealed generalized retinal thinning much more than a normal age-matched dog. Therefore, OCT scanning is considered to be a useful method for retinal evaluation in dogs with retinal degeneration.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.4
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• pp.216-221
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• 2011

Objective: To differentiate the human embryonic stem cells (hESCs) into the retinal pigment epithelium (RPE) in the defined culture condition and determine its therapeutic potential for the treatment of retinal degenerative diseases. Methods: The embryoid bodies were formed from hESCs and attached on the matrigel coated culture dishes. The neural structures consisting neural precursors were selected and expanded to form rosette structures. The mechanically isolated neural rosettes were differentiated into pigmented cells in the media comprised of N2 and B27. Expression profiles of markers related to RPE development were analyzed by reverse transcription-polymerase chain reaction and immunostaining. Dissociated putative RPE cells ($10^5$ cells/5 ${\mu}L$) were transplanted into the subretinal space of rat retinal degeneration model induced by intravenous sodium iodate injection. Animals were sacrificed at 1, 2, and 4 weeks after transplantation, and immnohistochemistry study was performed to verify the survival of the transplanted cells. Results: The putative RPE cells derived from hESC showed characteristics of the human RPE cells morphologically and expressed molecular markers and associated with RPE fate. Grafted RPE cells were found to survive in the subretinal space up to 4 weeks after transplantation, and the expression of RPE markers was confirmed with immunohistochemistry. Conclusion: Transplanted RPE cells derived from hESC in the defined culture condition successfully survived and migrated within subretinal space of rat retinal degeneration model. These results support the feasibility of the hESC derived RPE cells for cell-based therapies for retinal degenerative disease.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.65-73
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• 2023

Background: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina. Methods: To investigate the effects and underlying mechanisms of GBE on retinal damage in vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19 cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200 mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in vivo. Results: GBE significantly inhibited BL-induced cell damage in ARPE-19 cells by activating the SIRT1/PGC-1α pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-II, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1α pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in vivo. Conclusions: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.3
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• pp.229-235
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• 2013

Among several animal models of retinitis pigmentosa (RP), the more recently developed rd10 mouse with later onset and slower rate of retinal degeneration than rd1 mouse is a more suitable model for testing therapeutic modalities. We therefore investigated the time course of retinal degeneration in rd10 mice before adopting this model in our interventional studies. Electroretinogram (ERG) recordings were carried out in postnatal weeks (PW) 3~5 rd10 (n=23) and wild-type (wt) mice (n=26). We compared the amplitude and implicit time of the b-wave of ERG records from wt and rd10 mice. Our results showed that b-wave amplitudes in rd10 mice were significantly lower and the implicit time of b-waves in rd10 mice were also significantly slower than that in wt mice ($20{\sim}160{\mu}V$ vs. $350{\sim}480{\mu}V$; 55~75 ms vs. 100~150 ms: p<0.001) through PW3 to PW5. The most drastic changes in ERG amplitudes and latencies were observed during PW3 to PW4. In multichannel recording of rd10 retina in PW2 to PW4.5, we found no significant difference in mean spike frequency, but the frequency of power spectral peak of local field potential at PW3 and PW3.5 is significantly different among other age groups (p<0.05). Histologic examination of rd10 retinae showed significant decrease in thickness of the outer nuclear layer at PW3. TUNEL positive cells were most frequently observed at PW3. From these data, we confirm that in the rd10 mouse, the most precipitous retinal degeneration occurs between PW3~PW4 and that photoreceptor degeneration is complete by PW5.

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.291-297
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• 2022

Dry age-related macular degeneration (AMD) is a type of progressive blindness that is primarily due to dysfunction and the loss of retinal pigment epithelium (RPE). The accumulation of N-retinylidene-N-retinylethanolamine (A2E), a by-product of the visual cycle, causes RPE and photoreceptor degeneration that impairs vision. Genes associated with dry AMD have been identified using a blue light model of A2E accumulation in the retinal pigment epithelium and transcriptomic studies of retinal tissue from patients with AMD. However, dry macular degeneration progresses slowly, and current approaches cannot reveal changes in gene transcription according to stages of AMD progression. Thus, they are limited in terms of identifying genes responsible for pathogenesis. Here, we created a model of long-term exposure to identify temporally-dependent changes in gene expression induced in human retinal pigment epithelial cells (ARPE-19) exposed to blue light and a non-cytotoxic dose of A2E for 120 days. We identified stage-specific genes at 40, 100, and 120 days, respectively. The expression of genes corresponding to epithelial-mesenchymal transition (EMT) during the early stage, glycolysis and angiogenesis during the middle stage, and apoptosis and inflammation pathways during the late stage was significantly altered by A2E and blue light. Changes in the expression of genes at the late stages of the EMT were similar to those found in human eyes with late-stage AMD. Our results provide further insight into the pathogenesis of dry AMD induced by blue light and a novel model in vitro with which relevant genes can be identified in the future.

• Applied Microscopy
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• v.28 no.3
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• pp.391-398
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• 1998

The morphological phenotype on ocellus of Drosophila rdgC mutant was observed with electron microscope. The result showed the particular phenotype that was not found in other retinal degenarative mutants. The most distinct difference was the orientation of photoreceptor cells. The photoreceptor cells did not attached to corneagenous cells but dropped under corneagenous cells and assembled around newly formed space. Enormous multivesicle bodies caused by the degeneration of photoreceptor cells were frequently found. Rhabdomeres were also severely degenerated in consequence of the mutant. Another degeneration was found in a part of photoreceptor cell, but the degeneration of subrhabdomeric cisternae (SRC) was not found. It was a ovious difference of rdgC comparing with other two retinal degenerative mutants, rdgA and rdgB. As a result, rdgC mutant was affected on the attachment between photoreceptor cells and corneageneous cells, and it suggested the defect of cell-cell attachment. In addition, rdgC mutant was accompanied by the defect not only in retina but nerve system. The results were agreed to the reference discussion that the rdgC molecule is exist in the nerve.

• Journal of Veterinary Clinics
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• v.32 no.2
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• pp.209-211
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• 2015

A 5-year-old Siamese cat was presented at the Veterinary Medical Teaching Hospital in Seoul National University with visual impairment. The cat was blind and its pupillary light reflexes were sluggish OU. While there were no remarkable findings in the anterior segment, generalized tapetal hyperreflectivity and retinal vascular attenuation were observed in the posterior segment of both eyes. Any historical significance and clinical symptoms suggestive of infection or inflammation were absent. All of the above findings strongly indicated a diagnosis of hereditary retinal degeneration in the cat. This clinical case report demonstrates the possibility of the presence of feline hereditary retinal degeneration in Korea. Awareness of the condition should be raised to prevent the spread of hereditary retinopathy in the Korean cat population.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.167-175
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• 2015

A retinal prosthesis is being developed for the restoration of vision in patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electrical stimulation parameters for the prosthesis is one of the most important elements for the development of a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasic pulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinal degeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches were placed ganglion cell layer down onto an $8{\times}8$ multielectrode array (MEA) and RGC responses were recorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the same with symmetric pulse but the amplitude of 2nd phase of the pulse is less than $10{\mu}A$ and charge balanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration) modulation, duration (or amplitude) of the pulse was fixed to $500{\mu}s$($30{\mu}A$), changing the intensities (or duration) from 2 to $60{\mu}A$(60 to $1000{\mu}s$). RGCs were classified as response-positive when PSTH showed multiple (3~4) peaks within 400 ms post stimulus and the number of spikes was at least 30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulated both with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses produced significantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetry of the pulse.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.415-422
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• 2011

Previously, we reported that besides retinal ganglion cell (RGC) spike, there is ~10 Hz oscillatory rhythmic activity in local field potential (LFP) in retinal degeneration model, rd1 mice. The more recently identified rd10 mice have a later onset and slower rate of photoreceptor degeneration than the rd1 mice, providing more therapeutic potential. In this study, before adapting rd10 mice as a new animal model for our electrical stimulation study, we investigated electrical characteristics of rd10 mice. From the raw waveform of recording using $8{\times}8$ microelectrode array (MEA) from in vitro-whole mount retina, RGC spikes and LFP were isolated by using different filter setting. Fourier transform was performed for detection of frequency of bursting RGC spikes and oscillatory field potential (OFP). In rd1 mice, ~10 Hz rhythmic burst of spontaneous RGC spikes is always phase-locked with the OFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, there is a strong phase-locking tendency between the spectral peak of bursting RGC spikes (~5 Hz) and the first peak of OFP (~5 Hz) across different age groups. But this phase-locking property is not robust as in rd1 retina, but maintains for a few seconds. Since rd1 and rd10 retina show phase-locking property at different frequency (~10 Hz vs. ~5 Hz), we expect different response patterns to electrical stimulus between rd1 and rd10 retina. Therefore, to extract optimal stimulation parameters in rd10 retina, first we might define selection criteria for responding rd10 ganglion cells to electrical stimulus.