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

To investigate associations between central visual function and inner retinal structure in primary open-angle glaucoma (POAG). This study enrolled 78 POAG patients and 58 healthy controls. POAG was classified into early glaucoma and moderate to advanced glaucoma. The following tests were performed on all participants: isolated-check visual evoked potential (icVEP) testing, 24-2 standard automated perimetry (SAP), and Cirrus optical coherence tomography (OCT) examinations. Signal-to-noise ratio (SNR) measures obtained from icVEP responses to isolated checks presented at four depths of modulation (DOMs; 8%, 14%, 22%, and 32%) were explored. Mean macular sensitivity (mMS) was assessed by calculating the mean sensitivities of central 12 SAP points. Ganglion cell layer+ inner plexiform layer thickness (GCL+IPLT) and peripapillary retinal nerve fiber layer thickness (pRNFLT) were measured by OCT scanning. For each group of subjects, linear relationships among the following measures were analyzed: SNR, mMS, GCL+IPLT, and pRNFLT. SNR, mMS, GCL+IPLT, and pRNFLT were all more significantly decreased in glaucoma than in controls (P<0.001). A significant positive association was found between SNR at 14% DOM and GCL+IPLT at the inferior sector in early glaucoma (r=0.465, P=0.004). In moderate to advanced glaucoma, significant correlations were found between SNR at 32% DOM and mean GCL+IPLT (r=0.364, P=0.023), superior GCL+IPLT (r=0.358, P=0.025), and mean pRNFLT (r=0.396, P=0.025). In addition, in moderate to advanced glaucoma, there were significant correlations between mMS and all relevant measures of retinal thickness (r=0.330-0.663, P< 0.010). In early glaucoma, significant correlations were found between mean mMS and minimum GCL+IPLT (r=0.373, P=0.023), and between inferior mMS and superior GCL+IPLT (r=0.470, P=0.003). Linear models provided a good explanation for the relationship between SNR and inner retinal thickness (IRT), whereas nonlinear models better explained the relationship between mMS and IRT. In early glaucoma, both SNR and mMS were related moderately and significantly to IRT, whereas in moderate to advanced glaucoma, mMS was more strongly correlated with IRT than SNR.
Adult ; Aged ; Evoked Potentials, Visual/physiology* ; Female ; Glaucoma, Open-Angle/physiopathology* ; Humans ; Macula Lutea/physiopathology* ; Male ; Middle Aged ; Retina/physiopathology* ; Signal-To-Noise Ratio ; Tomography, Optical Coherence

The present study was designed to analyze the metabolites of all-trans-retinal (atRal) and compare the cytotoxicity of atRal versus its derivative all-trans-retinoic acid (atRA) in human retinal pigment epithelial (RPE) cells. We confirmed that atRA was produced in normal pig neural retina and RPE. The amount of all-trans-retinol (atROL) converted from atRal was about 2.7 times that of atRal-derived atRA after incubating RPE cells with 10 μmol/L atRal for 24 h, whereas atRA in medium supernatant is more plentiful (91 vs. 29 pmol/mL), suggesting that atRA conversion facilitates elimination of excess atRal in the retina. Moreover, we found that mRNA expression of retinoic acid-specific hydroxylase CYP26b1 was dose-dependently up-regulated by atRal exposure in RPE cells, indicating that atRA inactivation may be also initiated in atRal-accumulated RPE cells. Our data show that atRA-caused viability inhibition was evidently reduced compared with the equal concentration of its precursor atRal. Excess accumulation of atRal provoked intracellular reactive oxygen species (ROS) overproduction, heme oxygenase-1 (HO-1) expression, and increased cleaved poly(ADP-ribose) polymerase 1 (PARP1) expression in RPE cells. In contrast, comparable dosage of atRA-induced oxidative stress was much weaker, and it could not activate apoptosis in RPE cells. These results suggest that atRA generation is an antidotal metabolism pathway for atRal in the retina. Moreover, we found that in the eyes of ABCA4^-/-RDH8^-/- mice, a mouse model with atRal accumulation in the retina, the atRA content was almost the same as that in the wild type. It is possible that atRal accumulation simultaneously and equally promotes atRA synthesis and clearance in eyes of ABCA4^-/-RDH8^-/- mice, thus inhibiting the further increase of atRA in the retina. Our present study provides further insights into atRal clearance in the retina.
ATP-Binding Cassette Transporters/physiology* ; Alcohol Oxidoreductases/physiology* ; Animals ; Cell Survival/drug effects* ; Cells, Cultured ; Humans ; Inactivation, Metabolic ; Mice ; Retina/metabolism* ; Retinal Pigment Epithelium/metabolism* ; Swine ; Tretinoin/pharmacology*

BACKGROUNDRetinal degenerative diseases are the leading causes of blindness in developed world. Retinal progenitor cells (RPCs) play a key role in retina restoration. Triamcinolone acetonide (TA) is widely used for the treatment of retinal degenerative diseases. In this study, we investigated the role of TA on RPCs in hypoxia condition.

METHODSRPCs were primary cultured and identified by immunofluorescence staining. Cells were cultured under normoxia, hypoxia 6 h, and hypoxia 6 h with TA treatment conditions. For the TA treatment groups, after being cultured under hypoxia condition for 6 h, RPCs were treated with different concentrations of TA for 48-72 h. Cell viability was measured by cell counting kit-8 (CCK-8) assay. Cell cycle was detected by flow cytometry. Western blotting was employed to examine the expression of cyclin D1, Akt, p-Akt, nuclear factor (NF)-κB p65, and caspase-3.

RESULTSCCK-8 assays indicated that the viability of RPCs treated with 0.01 mg/ml TA in hypoxia group was improved after 48 h, comparing with control group (P < 0.05). After 72 h, the cell viability was enhanced in both 0.01 mg/ml and 0.02 mg/ml TA groups compared with control group (all P < 0.05). Flow cytometry revealed that there were more cells in S-phase in hypoxia 6 h group than in normoxia control group (P < 0.05). RPCs in S and G2/M phases decreased in groups given TA, comparing with other groups (all P < 0.05). There was no significant difference in the total Akt protein expression among different groups, whereas upregulation of p-Akt and NF-κB p65 protein expression and downregulation of caspase-3 and cyclin D1 protein expression were observed in 0.01 mg/ml TA group, comparing with hypoxia 6 h group and control group (all P < 0.05).

CONCLUSIONLow-dose TA has anti-apoptosis effect on RPCs while it has no stimulatory effect on cell proliferation.

Animals ; Apoptosis ; drug effects ; physiology ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; physiology ; Cell Hypoxia ; drug effects ; physiology ; Cell Proliferation ; drug effects ; physiology ; Cell Survival ; drug effects ; physiology ; Cells, Cultured ; Cyclin D1 ; metabolism ; NF-kappa B ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Retina ; cytology ; Stem Cells ; cytology ; drug effects ; Triamcinolone Acetonide ; pharmacology

The aim of this study was to investigate the acute effects of ethanol administration on pattern-reversal visual evoked potential (VEP) and multifocal electroretinography (mfERG). Fifteen healthy subjects with no ocular or general disease were recruited. VEP (0.25° pattern sizes) and mfERG with 19 elements in two recording segments were performed before ethanol administration to obtain baseline for each participant. A few days later, the participants visited again for VEP and mfERG measurements after ethanol administration. Ethanol (0.75 g/kg) was administered orally over the course of 30 minutes. VEP and blood alcohol concentration were evaluated one hour after ethanol administration, and mfERG was conducted after pupil dilation. The Wilcoxon signed-rank test was used to compare parameter changes after randomized eye selection. The mean blood alcohol concentration was 0.034% ± 0.05% by volume. VEP revealed a P100 latency delay (109.4 ± 5.3; 113.1 ± 8.2; P = 0.008) after alcohol administration. The P1 implicit time of ring 1 on mfERG showed a trend of shortening after alcohol administration (37.9 ± 1.0; 37.2 ± 1.5; P = 0.048). However, the changes did not show statistical significance after Bonferroni correction. In conclusion, orally administrated ethanol (0.75 g/kg) appears to suppress the central nervous system, but it is not clear whether alcohol intake affects the retina.
Adult ; *Alcohol Drinking ; Electroretinography ; Evoked Potentials, Visual/*physiology ; Female ; Humans ; Male ; Retina/physiology

No abstract available.
Aged ; Diagnosis, Differential ; Female ; Fluorescein Angiography ; Fundus Oculi ; Humans ; *Intraocular Pressure ; Regional Blood Flow/*physiology ; Retina/*diagnostic imaging ; Retinal Hemorrhage/*diagnosis/physiopathology ; Retinal Vein Occlusion/*diagnosis

OBJECTIVE: To compare pattern-pulse multifocal visual evoked potential (PPmfVEP) with pattern-reversal multifocal visual evoked potential (PRmfVEP), and to investigate the symmetry of mfVEP between both eyes in normal individuals. METHODS: The multifocal Vision Monitor was used to observe the mfVEP. T-test and ANOVA were used to analyze P1 wave, amplitude and signal noise ratios (SNR) of two mfVEPs. RESULTS: The SNR and the P1 amplitude reached the maximum at the central visual field and decreased with the increase of eccentricity, and then decreased slowly. The amplitude of the PPmfVEP was significantly smaller than the PRmfVEP in the central retina, while in the peripheral retina the result was exactly the opposite. SNR and amplitude of the PRmfVEP showed no statistical difference in both eyes (P > 0.05). The variance of the amplitude at the same side of visual field was larger than that at the symmetrical visual quadrant. CONCLUSION mfVEP can reflect the visual function in different parts of retina objectively and exactly. PPmfVEP reflect the vision function of the central retina better than PRmfVEP. The stability of PPmfVEP is better than PRmfVEP in the central retina, while the result is opposite in the peripheral retina. The mfVEP is symmetrical in both eyes of the same individual.
Evoked Potentials, Visual/physiology* ; Humans ; Neurologic Examination ; Reference Values ; Retina ; Sensitivity and Specificity ; Visual Fields/physiology*

PURPOSE: To compare the clinical characteristics of unilaterally progressing glaucoma (UPG) and simultaneously bilaterally progressing glaucoma (BPG) in medically treated cases. METHODS: Primary open angle glaucoma patients were classified as having UPG or BPG according to an assessment of optic disc and retinal nerve fiber layer photographs and visual field analysis. Risk factors including the presence of systemic diseases (hypertension, diabetes, cerebrovascular accident, migraine, and dyslipidema) were compared between the UPG and BPG groups. Baseline characteristics and pre- and post-treatment intraocular pressure (IOP) were compared between the progressing eye (PE) and the non-progressing eye (NPE) within the same patient in the UPG group and between the faster progressing eye and the slower progressing eye in the BPG group. RESULTS: Among 343 patients (average follow-up period of 4.2 years), 43 were categorized into the UPG group and 31 into the BPG group. The prevalence of all analyzed systemic diseases did not differ between the two groups. PEs in the UPG group had more severe pathology in terms of baseline visual field parameters than NPEs (mean deviation -6.9 ± 5.7 vs. -2.9 ± 3.9 dB, respectively; p < 0.001). However, baseline IOP, mean follow-up IOP, and other clinical characteristics were not significantly different between the PE and the NPE in the UPG group. The progression rate was significantly higher in the faster progressing eye in patients with BPG than in the PE for patients with UPG (-3.43 ± 3.27 vs. -0.70 ± 1.26 dB/yr, respectively; p = 0.014). CONCLUSIONS: There were no significant differences in the prevalence of systemic diseases between the UPG and BPG groups. Simultaneously bilaterally progressing patients showed much faster progression rates than those with a unilaterally progressing eye.
Disease Progression ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/*diagnosis/physiopathology ; Humans ; Intraocular Pressure/*physiology ; Male ; Middle Aged ; Optic Disk/*pathology ; Retina/*pathology ; Retrospective Studies ; Time Factors ; Visual Fields/*physiology

PURPOSE: We compared the abilities of Stratus optical coherence tomography (OCT), Heidelberg retinal tomography (HRT) and standard automated perimetry (SAP) to detect the progression of normal tension glaucoma (NTG) in patients whose eyes displayed localized retinal nerve fiber layer (RNFL) defect enlargements. METHODS: One hundred four NTG patients were selected who met the selection criteria: a localized RNFL defect visible on red-free fundus photography, a minimum of five years of follow-up, and a minimum of five reliable SAP, Stratus OCT and HRT tests. Tests which detected progression at any visit during the 5-year follow-up were identified, and patients were further classified according to the state of the glaucoma using the mean deviation (MD) of SAP. For each test, the overall rates of change were calculated for parameters that differed significantly between patients with and without NTG progression. RESULTS: Forty-seven (45%) out of 104 eyes displayed progression that could be detected by red-free fundus photography. Progression was detected in 27 (57%) eyes using SAP, 19 (40%) eyes using OCT, and 17 (36%) eyes using HRT. In early NTG, SAP detected progression in 44% of eyes, and this increased to 70% in advanced NTG. In contrast, OCT and HRT detected progression in 50 and 7% of eyes during early NTG, but only 30 and 0% of eyes in advanced NTG, respectively. Among several parameters, the rates of change that differed significantly between patients with and without progression were the MD of SAP (p = 0.013), and the inferior RNFL thickness (p = 0.041) and average RNFL thickness (p = 0.032) determined by OCT. CONCLUSIONS: SAP had a higher detection rate of NTG progression than other tests, especially in patients with advanced glaucoma, when we defined progression as the enlargement of a localized RNFL defect. The rates of change of the MD of SAP, inferior RNFL thickness, and average RNFL thickness differed between NTG patients with and without progression.
Disease Progression ; Female ; Humans ; Intraocular Pressure/*physiology ; Low Tension Glaucoma/*diagnosis/physiopathology ; Male ; Middle Aged ; Retina/*pathology ; Tomography, Optical Coherence/*methods ; Visual Field Tests/*methods ; Visual Fields/*physiology

The purpose of the present study was to establish normal electroretinogram (ERG) parameters using 56 normal eyes of four dog breeds common in Thailand: poodle, Labrador retriever, Thai ridgeback, and Thai Bangkaew. Standard ERG findings were bilaterally recorded using a handheld multi-species ERG unit with an ERG-jet lens electrode for 28 dogs under preanesthesia with diazepam, anesthesia with propofol, and anesthesia maintenance with isoflurane. There were significant differences in the mean values of ERG amplitudes and implicit times among the four dog breeds (p < 0.05) except for the b-wave implicit time of the photopic 30 Hz flicker response with 3 cd.s/m2 (p = 0.610). Out of the four breeds, Thai Bangkaew had the longest implicit time (p < 0.001) of scotopic low intensity responses, b-wave of scotopic standard intensity responses (3 cd.s/m2), a-wave of the higher intensity response (10 cd.s/m2), and a-wave of the photopic single flash response (3 cd.s/m2). For the b/a ratio, only the ratio of the Cone response was significantly different among the different breeds. In this summary, normal ERG parameters for four dog breeds were reported. Data from the investigation supported the hypothesis that determination of breed-specific limits of normality for ERG responses is necessary for individual clinics and laboratories.
Animals ; Dogs/genetics/*physiology ; Electroretinography/veterinary ; Reference Values ; Retina/*physiology