Exploring Embryo-Ototoxic Effects: Insights into Deodorant-Induced Hair Cell Damage in Zebrafish.

Our study investigated the embryo-ototoxic effects of deodorant2 (DA2) on zebrafish embryos, which serve as valuable model organisms due to genetic and physiological similarities to humans. We focused on understanding DA2's impact on zebrafish hair cells, which are vital for sensory perception and balance regulation. DA2, provided by the Ministry of Environment, Republic of Korea, was used at 460 µg/mL in dimethyl sulfoxide (DMSO), with a 0.43% DMSO solvent control group. Three experiments, each using 10 zebrafish specimens from each group, showed an initial 13% hair cell count reduction in the DA2-exposed group. Subsequent experiments demonstrated reductions of 37% and 22%, each with one mortality case. Statistical analysis revealed a significant 24% hair cell count reduction in the DA2-exposed group. We also assessed DA2's impact on zebrafish behavior. Although not statistically significant, differences in distances traveled (0.33-0.39, 95% confidence interval: -0.46-1.1, p = 0.2033) and latencies (-0.016-0.018, 95% confidence interval: -0.052-0.021, p = 0.1917) hinted at negative effects. These results highlight DA2's ototoxic properties affecting zebrafish auditory systems and behavior. Further investigation into DA2's effects on aquatic organisms and potential mitigation strategies are essential. These findings contribute to understanding DA2's safety profile, benefiting aquatic ecosystems and human health assessments.

CHANGES IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND DISEASE ACTIVITY IN TYPE 3 NEOVASCULARIZATION AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

PURPOSE: To investigate disease activity in patients with Type 3 neovascularization undergoing anti-vascular endothelial growth factor treatment through image analysis using optical coherence tomography angiography (OCTA). METHODS: Thirty-nine treatment-naive eyes with Type 3 neovascularization were included in the retrospective analysis. All patients were treated with three loading injections of an anti-vascular endothelial growth factor agent, followed by further injections as needed. Changes in the Type 3 lesion were analyzed through OCTA imaging during the 12 months of follow-up. RESULTS: The high-flow signal of Type 3 neovascularization on OCTA images disappeared in 46.2% eyes (19 of 39) and was persistent in 53.8% eyes (20 of 39) after loading injections. A persistent high-flow signal on OCTA after treatment was found at the sub-retinal pigment epithelium in 65.0% eyes (13 of 20), deep vascular plexus in 30.0% eyes (6 of 20), and outer neurosensory retina in 15.0% eyes (3 of 20). Eyes without lesions on OCTA images received significantly fewer injections (3.7 vs. 5.5; P = 0.016) and showed a longer retreatment-free period (mean 7.57 vs. 4.07 months; P = 0.002) during the 12-month follow-up than eyes with a persistent high-flow signal on OCTA. However, no significant between-group difference was observed in terms of improved visual acuity. CONCLUSION: Patients with Type 3 neovascularization who had no lesion on an OCTA scan after anti-vascular endothelial growth factor treatment showed a lower recurrence rate and maintained visual acuity with fewer injections than those with persistent high-flow lesions on an OCTA scan. Optical coherence tomography angiography may provide an additional biomarker for clinical guidance in the treatment and monitoring of disease activity in Type 3 neovascularization.

Correction to: Intravitreal bevacizumab injections combined with laser photocoagulation for adult-onset Coats' disease.

The IRB number of the published article was A-2015-016 (page 1512, 1st paragraph of the method section).

Do Disruptions in the Circadian Timing System Contribute to Autonomic Dysfunction in Huntington's Disease?

Huntington's disease (HD) patients suffer from a progressive neurodegenerative disorder that inflicts both motor and non-motor symptoms. HD is caused by a CAG repeat expansion within the first exon of the huntingtin (HTT) gene that produces a polyglutamine repeat that leads to protein misfolding, soluble aggregates, and inclusion bodies detected throughout the body. Both clinical and preclinical research indicate that cardiovascular dysfunction should be considered a core symptom in at least a subset of HD patients. There is strong evidence for dysautonomia (dysfunctional autonomic nervous system, ANS) in HD patients that can be detected early in the disease progression. The temporal patterning of ANS function is controlled by the circadian timing system based in the anterior hypothalamus. Patients with neurodegenerative diseases including HD exhibit disrupted sleep/wake cycle and, in preclinical models, there is compelling evidence that the circadian timing system is compromised early in the disease process. Here we review data from preclinical models of HD that explore the intersection between disruption of circadian rhythms and dysautonomia. This work will lead to new therapeutic strategies and standards of care for HD and other neurodegenerative diseases.

In vivo assay of the potential gadolinium-induced toxicity for sensory hair cells using a zebrafish animal model.

Recently, intratympanic injection of gadolinium-based contrast agent (GdC) is growing in use to visualize the endolymphatic hydrops. Although GdC has been quite safely used over 20 years through intravenous injection, the biological influence of GdC on sensory hair cells needs to be thoroughly assessed for wider clinical application of it through intratympanic injection. In this in vivo experimental study, the summated number of sensory hair cells (SO1, SO2, O1 and OC1 neuromasts) showed a steep decrease in the group exposed to 10% and 20% GdC (35.7 ± 7.3, 15.09 ± 10.82, respectively, P < .01) compared with the control group (47.18 ± 2.30). An increase in apoptosis was also observed in the group exposed to 20% gadolinium (7.20 ± 5.56), as compared with the control group (0.08 ± 0.72) or the group exposed to 10% gadolinium (3.48 ± 3.32). A significant reduction in the viable cytoplasmic mitochondria was observed in embryos exposed to 20% GdC (369 ± 124 µm2 , P = .01) as compared with control embryos (447 ± 118 µm2 ) or embryos exposed to 10% GdC (420 ± 108 µm2 ). GdC administration did not impact peripheral neural structures. GdC caused a significant reduction in sensory hair cell counts in response to high concentrations along with increased apoptosis and mitochondrial damage. However, it may not be likely that GdC will lead to hair cell toxicity, as the estimated concentration in the inner ear after clinically tried intratympanic injection is far more diluted than the non-toxic concentration (0.625%) that was tested in this study.

Intravitreal bevacizumab injections combined with laser photocoagulation for adult-onset Coats' disease.

PURPOSE: To evaluate the efficacy of intravitreal bevacizumab injections combined with laser photocoagulation in the treatment of adult-onset Coats' disease. METHODS: Thirteen eyes of 13 patients suffering from adult-onset Coats' disease were retrospectively included and analyzed. All patients were treated at baseline using intravitreal bevacizumab injections combined with laser photocoagulation. Follow-up treatment was performed as necessary. RESULTS: The mean age of the subjects was 40.3 years, and the mean follow-up period was 24.8 months. The mean number of bevacizumab injections was 2.69, and the mean number of laser treatment sessions was 1.68. The mean baseline best-corrected visual acuity (BCVA) was 0.72 logarithm of the minimum angle of resolution (logMAR; 20/104 Snellen equivalent), while the mean BCVA at the final visit was 0.68 logMAR (20/95; P = 0.548). In three patients (23.0 %), BCVA had improved by more than 3 lines, and seven patients (54.0 %) showed stable BCVA (changes within 2 lines of visual acuity) after treatment. The mean central foveal thickness improved significantly, from 473 µm at baseline to 288 µm at the final visit (P = 0.023). Final BCVA was significantly correlated with a baseline BCVA (P < 0.001; ρ = 0.882). The final BCVA of patients who had subfoveal hard exudates at baseline was significantly worse than that of patients without such exudates (P = 0.005). CONCLUSIONS: Intravitreal bevacizumab injection combined with laser photocoagulation may be an effective treatment option for adult-onset Coats' disease. Both poor initial BCVA and the occurrence of subfoveal hard exudates at baseline were associated with poor prognosis and poor therapeutic response.

Protective effects of Y-27632 against cisplatin-induced ototoxicity: A zebrafish model Y-27632 and cisplatin-induced ototoxicity.

Cisplatin is an effective chemotherapy agent against various solid malignancies; however, it is associated with irreversible bilateral sensorineural hearing loss, emphasizing the need for drug development to prevent this complication, with the current options being very limited. Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine protein kinase involved in various cellular processes, including apoptosis regulation. In this study, we used a transgenic zebrafish model (Brn3C: EGFP) in which hair cells within neuromasts are observed in green under fluorescent microscopy without the need for staining. Zebrafish larvae were exposed to cisplatin alone or in combination with various concentrations of Y-27632, a potent ROCK inhibitor. Hair cell counts, apoptosis assessments using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, FM1-43FX labeling assay and behavioral analyses (startle response and rheotaxis) were performed to evaluate the protective effects of Y-27632 against cisplatin-induced ototoxicity. Cisplatin treatment reduced the number of hair cells in neuromasts, induced apoptosis, and impaired zebrafish larval behaviors. Y-27632 demonstrated a dose-dependent protective effect against cisplatin-induced hair cell loss and apoptosis. These findings suggest that Y-27632, as a ROCK inhibitor, mitigates cisplatin-induced hair cell loss and associated ototoxicity in zebrafish.

Measuring Optokinetic Reflex and Vestibulo-Ocular Reflex in Unilateral Vestibular Organ Damage Model of Zebrafish.

One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.

Evaluation of structural and functional changes in non-pathologic myopic fundus using multifocal electroretinogram and optical coherence tomography.

PURPOSE: To evaluate structural and functional changes in non-pathologic myopic fundus using multifocal electroretinogram (mfERG) and spectral domain-optical coherence tomography (SD-OCT). METHODS: A total of 90 myopic subjects underwent mfERG and SD-OCT. The subjects were divided into four groups according to spherical equivalent refractive error: Group 1 (-0.50 to -2.75 D), Group 2 (-3.00 to -5.75 D), Group 3 (-6.00 to -9.75 D), and Group 4 (-10.0 to -15.0 D). Total retinal thickness, photoreceptor retinal thickness (PR), outer nuclear retinal thickness and mid-inner retinal thickness (MIR) were measured using SD-OCT in foveola and two perifoveal retinal regions 2.0 mm nasal and temporal from the foveola. The amplitude and implicit time of N1 and P1 mfERG responses were analyzed using six-concentric-ring grouping. Correlations between each retinal thickness, amplitude, and implicit time among the four myopic groups were analyzed. RESULTS: PR thickness in the foveola and MIR thickness in the perifoveal retina were significantly reduced with increasing myopic refractive errors (p = 0.001, respectively). Significant correlations appeared between N1 amplitude, P1 amplitude, P1 implicit time, and refractive errors (p = 0.001, respectively). Significant correlations appeared between MIR thickness and N1, P1 amplitude (p = 0.001, respectively) as well as N1, P1 implicit time (p = 0.02 and 0.03, respectively) in the perifoveal retina corresponding to ring 4. CONCLUSIONS: The correlation between structural and functional changes in myopia should be considered when interpreting retinal structure and function using SD-OCT and mfERG, especially in high myopia.

Extrafoveal changes following intravitreal bevacizumab injections for macular edema secondary to branch retinal vein occlusion: an mfERG and OCT study.

PURPOSE: To evaluate the functional and structural changes of extrafoveal macula after intravitreal bevacizumab (IVB) injection in patients with macular edema due to branch retinal vein occlusion (BRVO) using multifocal electroretinogram (mfERG) and optical coherence tomography (OCT). METHODS: A total of 19 eyes of 19 patients with macular edema due to BRVO received three consecutive IVB injections with a 6-week interval. Spectral domain optical coherence tomography (SD-OCT), mfERG, and fluorescein angiography (FA) were performed at baseline. The macular area was divided into four quadrants (Q1-Q4) based on FA. The mean retinal thickness (MRT) and mfERG parameters in each of the four quadrants were measured at baseline and 4 weeks after the third injection. RESULTS: The MRT in the four quadrants improved significantly after IVB injections (p < 0.01 for Q1 and Q2, p < 0.05 for Q3 and Q4) compared to baseline. The significant improvements in mfERG responses were seen in Q1 and Q2. In Q1, there were 68 and 56% improvement in N1 and P1 amplitude, respectively (p < 0.01). N1 and P1 amplitude in Q2 increased significantly by 43 and 46%, respectively, compared to baseline (p < 0.05). The MRT and P1 amplitude were significantly correlated at baseline in Q1 and Q2, but no significant correlations were found after three IVB injections. CONCLUSIONS: The injection of IVB improved functional and structural outcomes in the primarily affected half of the extrafoveal macula effectively. The measurements of structural and functional changes using mfERG and OCT may be appropriate for monitoring the effects of IVB injection in BRVO patients.

Protective effects of esomeprazole against cisplatin-induced ototoxicity: an in vitro and in vivo study.

In this study, we aimed to identify novel compounds that could afford protection against cisplatin-induced ototoxicity by employing both cell- and zebrafish (Danio rerio)-based screening platforms. We screened 923 US Food and Drug Administration-approved drugs to identify potential compounds exhibiting protective effects against cisplatin-induced ototoxicity in HEI-OC1 cells (auditory hair cell line). The screening strategy identified esomeprazole and dexlansoprazole as the primary hit compounds. Subsequently, we examined the effects of these compounds on cell viability and apoptosis. Our results revealed that esomeprazole and dexlansoprazole inhibited organic cation transporter 2 (OCT2), thus providing in vitro evidence that these compounds could ameliorate cisplatin-induced ototoxicity by directly inhibiting OCT2-mediated cisplatin transport. In vivo, the protective effects were validated using zebrafish; esomeprazole was found to decrease cisplatin-induced hair cell damage in neuromasts. Furthermore, the esomeprazole-treated group showed a significantly lower number of TUNEL-positive cells than the cisplatin-treated group. Collectively, our findings revealed that esomeprazole exerts a protective effect against cisplatin-induced hair cell damage in both HEI-OC1 cells and a zebrafish model.

Multiplex immunoassay platforms based on shape-coded poly(ethylene glycol) hydrogel microparticles incorporating acrylic acid.

A suspension protein microarray was developed using shape-coded poly(ethylene glycol) (PEG) hydrogel microparticles for potential applications in multiplex and high-throughput immunoassays. A simple photopatterning process produced various shapes of hydrogel micropatterns that were weakly bound to poly(dimethylsiloxane) (PDMS)-coated substrates. These micropatterns were easily detached from substrates during the washing process and were collected as non-spherical microparticles. Acrylic acids were incorporated into hydrogels, which could covalently immobilize proteins onto their surfaces due to the presence of carboxyl groups. The amount of immobilized protein increased with the amount of acrylic acid due to more available carboxyl groups. Saturation was reached at 25% v/v of acrylic acid. Immunoassays with IgG and IgM immobilized onto hydrogel microparticles were successfully performed with a linear concentration range from 0 to 500 ng/mL of anti-IgG and anti-IgM, respectively. Finally, a mixture of two different shapes of hydrogel microparticles immobilizing IgG (circle) and IgM (square) was prepared and it was demonstrated that simultaneous detection of two different target proteins was possible without cross-talk using same fluorescence indicator because each immunoassay was easily identified by the shapes of hydrogel microparticles.

Noise-induced hearing loss in zebrafish model: Characterization of tonotopy and sex-based differences.

Hearing loss caused by frequent and persistent exposure to loud noise is one of the most common diseases in modern society. Many studies have demonstrated the characteristics of noise-induced hearing loss in human and non-human vertebrate models, including frequency-specific noise-induced hearing loss and sex-biased differences. Zebrafish (Danio rerio) is a useful hearing research model because its lateral line is easy to access and because of its detailed perception of sound. Despite the increasing popularity of zebrafish as a model for NIHL, a better understanding of this model is needed to determine sex differences in NIHL. To study the features of zebrafish as they relate to an NIHL model, we tested various phenotypes after frequency-specific noise stimulation. The degree of damage to hair cells and hearing loss were investigated after exposing zebrafish to 200 Hz and 1 kHz continuous waves and broadband white noise with a bandwidth from 50 Hz to 1 kHz. After exposure to all frequencies, the larvae showed lateral line hair cell damage, which is superficially located. In adult zebrafish, the threshold of auditory-evoked potential signals is elevated. Moreover, the number of hair cells remarkably decreased in the rostral region of the saccule, after exposure to 1 kHz and white noise, whereas zebrafish exposed to 200 Hz noise showed a decrease in hair cells in the caudal region. Moreover, male zebrafish were found to be more vulnerable to noise than female zebrafish, as is the case in humans and other mammals. Cortisol levels also increased in the noise-exposed male group, as compared to the noise-exposed female and control male groups. However, there was no difference in cortisol levels when the noise-exposed female group was compared to the control female group. Our study demonstrates not only that noise-induced hearing loss is frequency-dependent but also that the degree of hearing loss is affected by sex in zebrafish, emphasizing the need to consider sex in NIHL studies.

Targeted Genetic Reduction of Mutant Huntingtin Lessens Cardiac Pathology in the BACHD Mouse Model of Huntington's Disease.

Individuals affected by Huntington's disease (HD) present with progressive degeneration that results in a wide range of symptoms, including cardiovascular (CV) dysfunction. The huntingtin gene (HTT) and its product are ubiquitously expressed, hence, the cardiomyopathy could also be driven by defects caused by its mutated form (mHTT) in the cardiomyocytes themselves. In the present study, we sought to determine the contribution of the mHTT expressed in the cardiomyocytes to CV symptoms. We utilized the BACHD mouse model, which exhibits many of the HD core symptoms, including CV dysfunction. This model allows the targeted genetic reduction of mHTT expression in the cardiomyocytes while maintaining the expression of the mHTT in the rest of the body. The BACHD line was crossed with a line of mice in which the expression of Cre recombinase is driven by the cardiac-specific alpha myosin-heavy chain (Myh6) promoter. The offspring of this cross (BMYO mice) exhibited a dramatic reduction in mHTT in the heart but not in the striatum. The BMYO mice were evaluated at 6 months old, as at this age, the BACHD line displays a strong CV phenotype. Echocardiogram measurements found improvement in the ejection fraction in the BMYO line compared to the BACHD, while hypertrophy was observed in both mutant lines. Next, we examined the expression of genes known to be upregulated during pathological cardiac hypertrophy. As measured by qPCR, the BMYO hearts exhibited significantly less expression of collagen1a as well as Gata4, and brain natriuretic peptide compared to the BACHD. Fibrosis in the hearts assessed by Masson's trichrome stain and the protein levels of fibronectin were reduced in the BMYO hearts compared to BACHD. Finally, we examined the performance of the mice on CV-sensitive motor tasks. Both the overall activity levels and grip strength were improved in the BMYO mice. Therefore, we conclude that the reduction of mHtt expression in the heart benefits CV function in the BACHD model, and suggest that cardiomyopathy should be considered in the treatment strategies for HD.

Analysis of behavioral changes in zebrafish (Danio rerio) larvae caused by aminoglycoside-induced damage to the lateral line and muscles.

Zebrafish behavior is influenced by the lateral line hair cells and muscles. Drug-induced behavioral changes can serve as indicators in the evaluation of drug toxicity. The aminoglycoside family of antibiotics comprise a number of agents, including neomycin (NM) and gentamicin (GM). We hypothesized that NM and GM exert different effects on zebrafish larvae through their action on the lateral line and muscle fibers, inducing different swimming behavioral patterns such as locomotor behavior and the startle response. In this study, 125 µM NM and 5, 10, 20 µM GM induced hair cell damage in the anterior and posterior lateral lines of zebrafish larvae. However, unlike GM, 125 µM NM also caused muscle damage. Locomotor behavior was decreased in the 125 µM NM-exposed group compared to the group exposed to GM. Furthermore, 125 µM NM exposure induced significantly different patterns of various indices of startle behavior compared with the GM exposure groups. Additionally, the larvae exhibited different startle responses depending on the concentration of GM. These results suggest that GM may be the drug-of-choice for analyzing behavioral changes in zebrafish caused by damage to the lateral line alone. Our study highlights the importance of confirming muscle damage in behavioral analyses using zebrafish.

Evaluation of Ototoxicity of an Antifog Agent and the Suspected Underlying Mechanisms: An Animal Study.

Use of rigid endoscopes has become widespread in middle ear surgeries, thereby attracting attention to the safety of antifog agents. However, few studies on the ototoxicity of antifog agents have been conducted. The purpose of this study was to evaluate hair cell damage and the underlying mechanisms caused by antifog agents using zebrafish larvae. We exposed zebrafish larvae at 3 days postfertilization to various concentrations of the antifog agent, Ultrastop (0.01, 0.02, 0.04, and 0.08%) for 72 hours. The average number of hair cells within 4 neuromasts of larvae, including supraorbital (SO1 and SO2), otic (O1), and occipital (OC1), in the control group were compared to those in the exposure groups. Significant hair cell loss was observed in the experimental groups compared to that in the control group (P < .01; control: 53.88 ± 4.85, 0.01%: 45.08 ± 11.70, 0.02%: 41.36 ± 12.00, 0.04%: 35.36 ± 16.18, and 0.08%: 15.60 ± 7.53 cells). Concentration-dependent increase in hair cell apoptosis by terminal deoxynucleotidyltransferase (TDT)-mediated dUTP-biotin nick end labeling assay (control: 0.00 ± 0.00, 0.01%: 3.48 ± 2.18, 0.02%: 9.64 ± 5.75, 0.04%: 17.72 ± 6.26, and 0.08%: 14.60 ± 8.18 cells) and decrease in the viability of hair cell mitochondria by 2-(4-[dimethylamino] styryl)-N-ethylpyridinium iodide assay (control: 9.61 ± 1.47, 0.01%: 8.28 ± 2.22, 0.02%: 8.45 ± 2.72, 0.04%: 7.25 ± 2.44, and 0.08%: 6.77 ± 3.26 percentage of total area) were observed. Antifog agent exposure can cause hair cell damage in zebrafish larvae, possibly by induction of mitochondrial damage with subsequent apoptosis of hair cells.

In vivo assay of the ethanol-induced embryonic hair cell loss and the protective role of the retinoic and folic acid in zebrafish larvae (Danio rerio).

In reference to the auditory manifestation of fetal alcohol syndrome, previous work has preferentially focused on the deviant neural development of the auditory system. Changes in the sensory hair cell, the ultimate sensory organ, were not well understood. In this study, we carried out an in vivo assessment of the embryonic hair cell changes on the lateral line of zebrafish upon exposure to various ethanol concentrations (0.25%, 0.5%, 0.75%, and 1.0%). A significant decrease in the hair cell count was confirmed as the ethanol concentration increased. Long-term observation (up to 240 hours post-fertilization [hpf]) suggested an irreversible hair cell loss with little chance of a simple delayed development. For an underlying biological process, a significant increase of hair cell apoptosis and a significant decrease of cytoplasmic mitochondria were confirmed as the ethanol concentration increased. Co-treatment with retinoic (0.1 nM) or folic (0.1 mM) acid with the same concentrations of ethanol resulted in significant increases in the remaining hair cells, compared to the ethanol-only treatment group, for every ethanol concentration. The retinoic acid provided more effective protection over folic acid, resulting in no significant changes in hair cell counts for every ethanol concentration (except 1.0%), compared with that of the negative control (without chemical treatment). Hair cell counts in every ethanol concentration were significantly lower than those in negative controls without chemical treatment after folic acid co-treatment. In conclusion, gestational ethanol exposure causes developmental sensory hair cell loss. Potential underlying mechanisms include retinoic or folic acid deficiency, and mitochondrial damage with subsequent hair cell apoptosis. Hair cell loss could possibly be prevented by administering either retinoic or folic acid, with retinoic acid supplementation as the preferred treatment.

Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Pachychoroid Neovasculopathy.

PURPOSE: To compare the effectiveness of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for pachychoroid neovasculopathy and neovascular age-related macular degeneration (AMD). METHODS: Twenty-two eyes with pachychoroid neovasculopathy and 183 eyes with neovascular AMD were retrospectively included for analysis. All patients were treatment naive and received an initial series of 3 monthly loading injections of anti-VEGF, followed by further injections as required. The visual and anatomical outcomes after treatment were evaluated at 12 months from baseline. RESULTS: The pachychoroid neovasculopathy group showed a significant improvement in the mean best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution) from 0.50 ± 0.32 (Snellen equivalent; 20/63) to 0.31 ± 0.28 (20/85, P = 0.021), and a decrease in the mean central foveal thickness from 373 ± 184 µm to 195 ± 137 µm at 12 months (P < 0.001). No significant intergroup difference in the achieved improvement of BCVA and decrease of central foveal thickness was observed. However, compared with the neovascular AMD group, the pachychoroid neovasculopathy group showed lower proportions of patients requiring retreatment during the maintenance phase (59.1% vs. 80.9%, P = 0.018), longer treatment-free period after loading injections (6.1 vs. 4.3 months, P = 0.006), and fewer number of injections (4.2 vs. 4.9, P = 0.031). CONCLUSIONS: Anti-VEGF treatment for pachychoroid neovasculopathy showed a similar efficacy to anti-VEGF treatment for neovascular AMD in improving visual acuity during 12 months. However, eyes with pachychoroid neovasculopathy had a significantly lesser need for retreatment during the maintenance phase and longer retreatment-free period, while requiring fewer injections.

Assessment of hair cell damage and developmental toxicity after fine particulate matter 2.5 µm (PM 2.5) exposure using zebrafish (Danio rerio) models.

OBJECTIVES: Particulate matter (PM) exposure has become one of the most serious problems. The aim of the present study was to evaluate the hair cell damage and possible developmental toxicity caused by PM2.5 exposure using a zebrafish model. METHODS: Zebrafish embryos were exposed to various concentrations of PM2.5. Developmental toxicity was evaluated based on general morphology score (GMS) system and Panzica-Kelly score, and by measurement of body length and heart rate. To evaluate hair cell damage, the average number of total hair cells within four neuromasts exposed to various concentrations of PM2.5 was compared with that of the control group. RESULTS: Morphological abnormalities evaluated by the GMS system and Panzica-Kelly score were rare and body length tended to be shorter in the PM2.5-exposed groups. Heart rate decreased significantly in the PM2.5-exposed group. Additionally, significant hair cell damage was observed after PM2.5 exposure. It was dose-dependent and more severe after a longer period exposure (10 dpf). CONCLUSIONS: In zebrafish embryos, exposure of PM2.5 in the early stages of life decreased heart rate and caused significant hair cell damage in a dose-dependent manner.