Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.
Animals ; Mice ; Dark Adaptation ; Light ; Retina ; Retinal Cone Photoreceptor Cells/metabolism* ; Adaptation, Ocular ; Neuroglia/physiology* ; Cell Communication ; Thyroid Hormones

PURPOSE: We investigated structural changes in the retina by using optical coherence tomography (OCT) in a feline model of retinal degeneration using iodoacetic acid (IAA).METHODS: We examined 22 eyes of 11 felines over 2 years of age. The felines had fasted for 12 hours and were intravenously injected with IAA 20 mg/kg of body weight. OCT (Spectralis OCT) was performed at the point where the ends of the retinal vessels collected in the lateral direction from the optic nerve head and area centralis. Similarly, OCT was performed four times at 1-week intervals following injections, at which point the felines were sacrificed and histologic examinations were performed. Using OCT, the thickness of each layer of the retina was measured.RESULTS: The average body weight of the three male and eight female felines investigated in this study was 1.61 ± 0.19 kg. The mean total retinal thickness of the felines before injection was 221.32 ± 9.82 µm, with a significant decrease in the retinal thickness at 2, 3, and 4 weeks following injections of 186.41 ± 35.42, 174.56 ± 31.94, and 175.35 ± 33.84 µm, respectively (p = 0.028, 0.027, and 0.027, respectively). The thickness of the outer nuclear layer was 57.49 ± 8.03 µm before injection and 29.26 ± 17.87, 25.62 ± 13.88, and 31.60 ± 18.38 µm at 2, 3, and 4 weeks, respectively, after injection (p = 0.028, 0.028, 0.046, respectively).CONCLUSIONS: In a feline model of retinal degeneration using IAA, the total retinal thickness and the thickness of the outer nuclear layer were shown to decrease significantly on OCT.
Angiography ; Body Weight ; Female ; Humans ; Iodoacetic Acid ; Male ; Optic Disk ; Photoreceptor Cells, Vertebrate ; Retina ; Retinal Degeneration ; Retinal Vessels ; Retinaldehyde ; Tomography, Optical Coherence

Spherical neural mass (SNM) is a mass of neural precursors that have been used to generate neuronal cells with advantages of long-term passaging capability with high yield, easy storage, and thawing. In this study, we differentiated neural retinal progenitor cells (RPCs) from human induced pluripotent stem cells (hiPSC)-derived SNMs. RPCs were differentiated from SNMs with a noggin/fibroblast growth factor-basic/Dickkopf-1/Insulin-like growth factor-1/fibroblast growth factor-9 protocol for three weeks. Human RPCs expressed eye field markers (Paired box 6) and early neural retinal markers (Ceh-10 homeodomain containing homolog), but did not photoreceptor marker (Opsin 1 short-wave-sensitive). Reverse transcription polymerase chain reaction revealed that early neural retinal markers (Mammalian achaete-scute complex homolog 1, mouse atonal homolog 5, neurogenic differentiation 1) and retinal fate markers (brain-specific homeobox/POU domain transcription factor 3B and recoverin) were upregulated, while the marker of retinal pigment epithelium (microphthalmia-associated transcription factor) only showed slight upregulation. Human RPCs were transplanted into mouse (adult 8 weeks old C57BL/6) retina. Cells transplanted into the mouse retina matured and expressed markers of mature retinal cells (Opsin 1 short-wave-sensitive) and human nuclei on immunohistochemistry three months after transplantation. Development of RPCs using SNMs may offer a fast and useful method for neural retinal cell differentiation.
Animals ; Cell Differentiation ; Humans* ; Immunohistochemistry ; Induced Pluripotent Stem Cells ; Methods ; Mice ; Neurons ; Photoreceptor Cells, Vertebrate ; Polymerase Chain Reaction ; Retina ; Retinal Pigment Epithelium ; Retinaldehyde* ; Reverse Transcription ; Stem Cells* ; Transcription Factors ; Up-Regulation

Solar retinopathy is an injury of the retinal photoreceptors due to excessive exposure to the solar radiation. Diagnosis of the disease is challenging and requires combination of a detailed history and imaging modalities. This case report focuses on a 55-year-old fruit picker with an irreversible central scotoma of the right eye. A diagnosis of solar retinopathy was made based on history but mainly by several imaging modalities, such as optical coherence tomography (OCT), infrared (IF) imaging of the fundus and fundus autofluorescence (FAF). Electroretinogram (ERG)showed flattened and reduced waves in both scotopic and photopic response. Fundus angiography (FA) revealed no obvious telangectatic vessels. In conclusion, solar retinopathy is a disease where multimodal imaging may play an important role in the diagnosis. The condition may be irreversible thus advocating protective eyewear is mandatory in patients who are chronically exposed to the sun.
Photoreceptor Cells, Vertebrate

PURPOSE: Sildenafil citrate, is an oral tablet demonstrating efficacy for maintaining an erection in males with erectile dysfunction by inhibiting phosphodiesterase type 5 (PDE5). In the present study, we report 1 case of a transient color anomaly with visual field defect after an overdose of sildenafil citrate. CASE SUMMARY: One patient, a 39-year-old female, with no significant medical history other than previous major depressive disorder, visited an outpatient department due to the visual field defect that began after taking 30 tablets of sildenafil citrate (50 mg) 3 days earlier. A number of ophthalmologic tests were administered including visual acuity test, color vision test, fundus photography and the measurement of retinal structure with optical coherent tomography and her condition was monitored. The best corrected visual acuity was 1.0 in both right and left eyes in her first visit. The color anomaly and a central scotoma of both eyes were detected in the visual field test, while significant signs were not observed after evaluation using optical coherent tomography and fundus photography. After 5 weeks, the visual acuity was not affected, the color anomaly symptom disappeared and the focal visual field defect was present although improved. CONCLUSIONS: Transient color anomaly and persistent central scotoma caused by an overdose ingestion of sildenafil has not been reported in Korea, The related mechanisms may involve the inhibition of PDE5 on ganglion cells and bipolar cells in the retina and interruption of phosphodiesterase type 6 (PDE6) function in both rods and cones.
Adult ; Citric Acid* ; Color Vision ; Cyclic Nucleotide Phosphodiesterases, Type 6 ; Depressive Disorder, Major ; Eating ; Erectile Dysfunction ; Female ; Ganglion Cysts ; Humans ; Korea ; Male ; Outpatients ; Photography ; Photoreceptor Cells, Vertebrate ; Retina ; Retinaldehyde ; Scotoma ; Tablets ; Visual Acuity ; Visual Field Tests ; Visual Fields* ; Sildenafil Citrate

PURPOSE: To investigate which spectral domain optical coherence tomography (SD-OCT) findings predict visual outcome after anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (NV-AMD). METHODS: We reviewed the medical records of patients with treatment-naive NV-AMD who underwent three or more consecutive anti-VEGF injections. The patients were divided into three groups according to their changes of visual acuity (VA); improved (group I), static (group S), or worsened (group W). We assessed the incidences and values of all available SD-OCT findings of these groups, compared these findings between the three groups and compared the initial values with the post-treatment values. RESULTS: Better initial VA and longer external limiting membrane (ELM) length were associated with less change in VA after anti-VEGF treatment. The initial VA was mildly correlated with initial photoreceptor inner and outer segment junction (IS/OS) length and initial ELM length. The final VA was also mildly correlated with the final IS/OS length and the final ELM length. VA was significantly changed after anti-VEGF treatment in groups W and I. With regard to incidence, disruption of the IS/OS (IS/OS-D), disruption of the ELM (ELM-D) and ELM length differed significantly between the three groups, particularly ELM-D. The incidences of IS/OS-D and ELM-D in group I were significantly lower than those in groups S and W, and those in group S were also lower than those in group W. The ELM length in group I was significantly longer than it was in groups S and W, and the ELM length in group S was longer than that for group W. However, these three findings did not change after the anti-VEGF treatment. CONCLUSIONS: Initial IS/OS-D, ELM length and particularly ELM-D can be useful predictors of the visual outcome after anti-VEGF treatment in NV-AMD patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*therapeutic use ; Choroidal Neovascularization/*drug therapy/physiopathology ; Female ; Humans ; Intravitreal Injections ; Male ; Middle Aged ; Ranibizumab/*therapeutic use ; Retinal Photoreceptor Cell Inner Segment/pathology ; Retinal Photoreceptor Cell Outer Segment/pathology ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/*physiology ; Wet Macular Degeneration/*drug therapy/physiopathology

The ubiquitous Na, K-ATPase is a membrane-bound ion pump located in the plasma membrane in all animal cells and plays an essential role in a variety of cellular functions. Studies in several organisms have shown that this protein regulates different aspects of embryonic development and is responsible for the pathogenesis of several human diseases. Na, K-ATPase is an important factor for retinal development, and combinations of the isoforms of each of its subunits are expressed in different cell types and determine its functional properties. In this study, we performed RT-PCR assay to determine temporal expression and in situ hybridization to determine spatial expression of Na, K-ATPase beta2 isoform (atp1b2) in Xenopus laevis. Focusing on retinal expression to distinguish the specific expression domain, we used retinal marker genes sox4, sox11, vsx1, and . Xenopus atp1b2 was expressed from late gastrulation to the tadpole stage. Using whole mount in situ hybridization, we showed that Xenopus atp1b2 was expressed broadly in the eye, the whole surface ectoderm, and gills. In situ hybridization on sections revealed detailed and specific expression in the outer nuclear layer of the retina, which consists of two major classes of photoreceptors, rods and cones, surface ectoderm, pharyngeal epithelium, and gills. These findings indicate that atp1b2 may play an important role for the development of Xenopus retina.
Animals ; Cell Membrane ; Ectoderm ; Embryonic Development ; Epithelium ; Female ; Gastrulation ; Gills ; Humans ; In Situ Hybridization ; Ion Pumps ; Larva ; Pregnancy ; Protein Isoforms ; Retina* ; Retinal Rod Photoreceptor Cells ; Retinaldehyde ; Xenopus laevis ; Xenopus*

PURPOSE: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) compared with observation for treating acute central serous chorioretinopathy (CSC). METHODS: A retrospective study of 36 patients with acute CSC, including 21 patients treated with anti-VEGF (anti-VEGF group) and 15 patients with observation (observation group). Patients in the anti-VEGF group received a single dose of bevacizumab or ranibizumab at baseline. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and resolution of subretinal fluid (SRF) on optical coherence tomography (OCT) were assessed. The integrity of the foveal inner segment/outer segment (IS/OS) line at 12 months was also analyzed. RESULTS: Resolution of SRF was achieved in 20 of 21 eyes in the anti-VEGF group and in 12 of 15 eyes in the observation group (p = 0.151). Mean BCVA and CFT were not different between the two groups at 12 months (p > 0.05). The amount of change in BCVA, however, differed significantly between the groups (p = 0.044). Final OCT more frequently detected the foveal IS/OS line in the anti-VEGF group than in the observation group (p = 0.012). CONCLUSIONS: In terms of BCVA, anti-VEGF and observation only had similar therapeutic effects in acute CSC patients. In some patients, however, the rapid resolution of SRF by anti-VEGF might reduce the risk of photoreceptor degeneration and improve long-term visual acuity.
Acute Disease ; Adult ; Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/therapeutic use ; Central Serous Chorioretinopathy/*drug therapy/physiopathology ; Female ; Humans ; Intravitreal Injections ; Male ; Middle Aged ; Observation ; Ranibizumab/therapeutic use ; Retinal Photoreceptor Cell Inner Segment/pathology ; Retinal Photoreceptor Cell Outer Segment/pathology ; Retrospective Studies ; Subretinal Fluid/drug effects ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity

PURPOSE: To report a case of oxaliplatin (Eloxatin(R))-related ocular toxicity in a patient with advanced stomach cancer. CASE SUMMARY: A 43-year-old female with advanced stomach cancer experienced visual symptoms during the treatment with oxaliplatin on a XELOX schedule (a combination of oxaliplatin and capecitabine). After 1 cycle of chemotherapy, she complained of blurred vision and visual field defects in both eyes. Visual field tests showed a bilateral concentric field defect and the electroretinogram revealed a marked reduction of responses in both eyes. On the second cycle of chemotherapy, oxaliplatin was discontinued due to suspicious ocular toxicity. Her visual symptoms improved and visual field test showed normal results 1 month after oxaliplatin discontinuation. However, 3 months after oxaliplatin discontinuation, electroretinogram remained abnormal despite the progressive improvement. CONCLUSIONS: Platinum-based antineoplastic agents such as oxaliplatin should be administered with caution because oxaliplatin can cause damage to the retinal photoreceptors and the optic nerve. Early detection of ocular toxicity and discontinuation of oxaliplatin therapy could prevent severe and irreversible visual loss.
Adult ; Antineoplastic Agents ; Appointments and Schedules ; Drug Therapy ; Female ; Humans ; Optic Nerve ; Photoreceptor Cells, Vertebrate ; Stomach Neoplasms ; Visual Field Tests ; Visual Fields

OBJECTIVE: To determine the relationship between hypothyroidism and color vision deficiency among Filipinos ages 20-60 years
DESIGN AND METHODS: A cross-sectional study was performed on 91 biochemically hypothyroid and euthyroid patients seen at the Makati Medical Center from July to December 2013. All subjects underwent the Ishihara color test, followed by the Farnsworth-Munsell D15 test if this was positive. The patient who tested positive in the Farnsworth-Munsell D15 test was referred to an ophthalmologist to rule out any anatomic problem, and was excluded from the study if found to have any. Fisher's exact test assessed the significant correlation between hypothyroidism and color vision deficiency. A p-value less than 0.05 was considered significant.
RESULTS: Of the 91 patients that were included in the study, the average age was 42 years, majority (87%) were females, and 41% were biochemically hypothyroid. All euthyroid patients (100%) had normal color vision, while one hypothyroid patient (3.0%) tested positive for color vision deficiency (p-value 0.407).
CONCLUSION: Based on this study, the hypothyroid state of the patients had no effect on their color vision, unlike those seen in rodents, probably because mature human cones are not as easily affected by changes in thyroid hormone levels.

Human ; Male ; Female ; Middle Aged ; Adult ; Color Vision Defects ; Color Vision ; Ophthalmologists ; Retinal Cone Photoreceptor Cells ; Thyroid Hormones ; Hypothyroidism