Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.

BACKGROUND: The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021. METHODS: We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination. RESULTS: Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement. CONCLUSIONS: Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes.

A common trajectory of gut microbiome development during the first month in healthy neonates with limited inter-individual environmental variations.

The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3-V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development.

Early Gut Microbiota Profile in Healthy Neonates: Microbiome Analysis of the First-Pass Meconium Using Next-Generation Sequencing Technology.

Gut microbiome development during early life has significant long-term effects on health later in life. The first-pass meconium is not sterile, and it is important to know the initial founder of the subsequent gut microbiome. However, there is limited data on the microbiota profile of the first-pass meconium in healthy neonates. To determine the early gut microbiota profile, we analyzed 39 samples of the first-pass meconium from healthy neonates using 16S rRNA sequencing. Our results showed a similar profile of the microbiota composition in the first-pass meconium samples. Pseudomonas was the most abundant genus in most samples. The evenness of the microbial communities in the first-pass meconium was extremely poor, and the average Shannon diversity index was 1.31. An analysis of the relationship between perinatal characteristics and the meconium microbiome revealed that primigravidae babies had a significantly higher Shannon diversity index (p = 0.041), and the Bacteroidales order was a biomarker for the first-pass meconium of these neonates. The Shannon diversity index was not affected by the mode of delivery, maternal intrapartum antibiotic treatment, prolonged rupture of membranes, or birth weight. Our study extends previous research with further characterization of the gut microbiome in very early life.

Risk of dialysis in patients receiving intravitreal anti-vascular endothelial growth factor treatment: a population-based cohort study.

We utilized the Longitudinal Health Insurance Database which was stemmed from the Taiwan's National Health Insurance Research Database to conduct a retrospective cohort study investigating the risk of becoming dialysis dependent after receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents for retinal diseases. Patients newly receiving intravitreal ranibizumab or aflibercept from 2000 to 2017 for age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusions, or myopic choroid neovascularization were included as the study group, and patients with same retinal diseases but did not receive intravitreal anti-VEGFs served as controls extracted by age- and sex-matched (1:4) and further propensity score matching (PSM). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the risk of dialysis. A cohort of 2447 anti-VEGF users and 2447 controls by PSM were evaluated. Higher dialysis risks were observed among patients newly receiving anti-VEGF agents compared to controls (adjusted HR: 1.849; 95% CI: 1.378-2.482) in the PSM cohort. For subgroup analysis, patients newly receiving anti-VEGF treatment for diabetic macular edema had significant risk (adjusted HR: 1.834; 95% CI: 1.448-2.324) of becoming dialysis-dependent, while patients in other subgroups demonstrated similar risks as the controls. In conclusion, intravitreal anti-VEGF agents might increase the risk of becoming dialysis-dependent, especially in patients who are treated for diabetic macular edema.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Susac Syndrome Following COVID-19 Vaccination: A Case Report.

Due to the COVID-19 pandemic, numerous vaccines have been developed for the disease. However, with large-scale vaccination has come the gradual emergence of immunological phenomena caused by these new vaccines. Herein, we report a 48-year-old female with a sudden onset of inferior visual field defects in the left eye following her first dose of the ChAdOx1 vaccine. Dilated fundus examination combined with optical coherence tomography and fluorescein angiography confirmed the diagnosis of branch retinal artery occlusion. Within 4 weeks following vaccination, symptoms associated with hearing impairment developed, and magnetic resonance imaging revealed leptomeningeal enhancement. The diagnosis of Susac syndrome (SS) was confirmed. The development of SS may be caused by endotheliopathy resulting from the molecular mimicry of the ChAdOx1 vaccine. Clinicians should be aware of the symptoms of SS, which may develop after COVID-19 vaccination. Further experimental surveillance and case-control studies are required to confirm this relationship.

Recombinant thrombomodulin domain 1 rescues pathological angiogenesis by inhibition of HIF-1α-VEGF pathway.

Pathological angiogenesis (PA) contributes to various ocular diseases, including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, which are major causes of blindness over the world. Current treatments focus on anti-vascular endothelial growth factor (VEGF) therapy, but persistent avascular retina, recurrent intravitreal neovascularization, and general adverse effects are reported. We have previously found that recombinant thrombomodulin domain 1 (rTMD1) can suppress vascular inflammation. However, the function of rTMD1 in VEGF-induced PA remains unknown. In this study, we found that rTMD1 inhibited VEGF-induced angiogenesis in vitro. In an oxygen induced retinopathy (OIR) animal model, rTMD1 treatment significantly decreased retinal neovascularization but spared normal physiological vessel growth. Furthermore, loss of TMD1 significantly promoted PA in OIR. Meanwhile, hypoxia-inducible factor-1α, the transcription factor that upregulates VEGF, was suppressed after rTMD1 treatment. The levels of interleukin-6, and intercellular adhesion molecule-1 were also significantly suppressed. In conclusion, our results indicate that rTMD1 not only has dual effects to suppress PA and inflammation in OIR, but also can be a potential HIF-1α inhibitor for clinical use. These data bring forth the possibility of rTMD1 as a novel therapeutic agent for PA.

NIgPred: Class-Specific Antibody Prediction for Linear B-Cell Epitopes Based on Heterogeneous Features and Machine-Learning Approaches.

Upon invasion by foreign pathogens, specific antibodies can identify specific foreign antigens and disable them. As a result of this ability, antibodies can help with vaccine production and food allergen detection in patients. Many studies have focused on predicting linear B-cell epitopes, but only two prediction tools are currently available to predict the sub-type of an epitope. NIgPred was developed as a prediction tool for IgA, IgE, and IgG. NIgPred integrates various heterologous features with machine-learning approaches. Differently from previous studies, our study considered peptide-characteristic correlation and autocorrelation features. Sixty kinds of classifier were applied to construct the best prediction model. Furthermore, the genetic algorithm and hill-climbing algorithm were used to select the most suitable features for improving the accuracy and reducing the time complexity of the training model. NIgPred was found to be superior to the currently available tools for predicting IgE epitopes and IgG epitopes on independent test sets. Moreover, NIgPred achieved a prediction accuracy of 100% for the IgG epitopes of a coronavirus data set. NIgPred is publicly available at our website.

The Incoherent Fluctuation of Folate Pools and Differential Regulation of Folate Enzymes Prioritize Nucleotide Supply in the Zebrafish Model Displaying Folate Deficiency-Induced Microphthalmia and Visual Defects.

OBJECTIVE: Congenital eye diseases are multi-factorial and usually cannot be cured. Therefore, proper preventive strategy and understanding the pathomechanism underlying these diseases become important. Deficiency in folate, a water-soluble vitamin B, has been associated with microphthalmia, a congenital eye disease characterized by abnormally small and malformed eyes. However, the causal-link and the underlying mechanism between folate and microphthalmia remain incompletely understood. METHODS: We examined the eye size, optomotor response, intracellular folate distribution, and the expression of folate-requiring enzymes in zebrafish larvae displaying folate deficiency (FD) and ocular defects. RESULTS: FD caused microphthalmia and impeded visual ability in zebrafish larvae, which were rescued by folate and dNTP supplementation. Cell cycle analysis revealed cell accumulation at S-phase and sub-G1 phase. Decreased cell proliferation and increased apoptosis were found in FD larvae during embryogenesis in a developmental timing-specific manner. Lowered methylenetetrahydrofolate reductase (mthfr) expression and up-regulated methylenetetrahydrofolate dehydrogenase (NADP+-dependent)-1-like (mthfd1L) expression were found in FD larvae. Knocking-down mthfd1L expression worsened FD-induced ocular anomalies; whereas increasing mthfd1L expression provided a protective effect. 5-CH3-THF is the most sensitive folate pool, whose levels were the most significantly reduced in response to FD; whereas 10-CHO-THF levels were less affected. 5-CHO-THF is the most effective folate adduct for rescuing FD-induced microphthalmia and defective visual ability. CONCLUSION: FD impeded nucleotides formation, impaired cell proliferation and differentiation, caused apoptosis and interfered active vitamin A production, contributing to ocular defects. The developmental timing-specific and incoherent fluctuation among folate adducts and increased expression of mthfd1L in response to FD reflect the context-dependent regulation of folate-mediated one-carbon metabolism, endowing the larvae to prioritize the essential biochemical pathways for supporting the continuous growth in response to folate depletion.

Author Correction: Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.

We investigated the temporal changes in major eye injuries in Taiwan by reviewing the medical records of all patients with ocular trauma hospitalized at the National Cheng Kung University Hospital during 2002-2004 and 2012-2014. A total of 169 eyes (161 patients) during 2002-2004 and 121 eyes (120 patients) during 2012-2014 were enrolled (mean ± SD age: 41.9 ± 20.8 years in 2002-2004, and 51.8 ± 19.3 years in 2012-2014). Males accounted for ~75% of patients. The most frequent injury-causing object was metallic material (~24%), and blunt traumas were most frequently attributable to traffic accidents and falls. The most common locations of injuries for males and females were the workplace and home, respectively. Open-globe injuries occurred in ~70% of eyes, requiring primary repair, cataract extraction, and/or intraocular lens implantation. The frequencies of fall injury, lacrimal system laceration, lens injury, corneal/scleral foreign bodies, and use of intracameral antibiotics increased from 2002-2004 to 2012-2014, while those of closed-globe injury, vitreous haemorrhage, optic nerve injury, and medical treatment decreased. The final visual acuity remained poor (≤20/200) in >1/3 of injured eyes. Despite therapeutic advancements, major eye injuries still pose a high risk for poor visual outcome.

Real-world use of ranibizumab for neovascular age-related macular degeneration in Taiwan.

This study investigated the "real-world" use of ranibizumab for neovascular age-related macular degeneration (nAMD) in Taiwan and assessed the visual outcome. We reviewed the medical records at National Cheng Kung University Hospital, Taiwan, during 2012-2014 for 264 consecutive eyes of 229 patients with nAMD, who applied for ranibizumab covered by national health insurance. A total of 194 eyes (73.5%) in 179 patients (65.5% men; mean ± standard deviation age 69.4 ± 10.7 years) were pre-approved for treatment. Applications for treatment increased year by year, but approval rates decreased during this time. The major causes of rejection for funding were diseases mimicking nAMD, including macular pucker/epiretinal membrane, macular scarring, dry-type AMD, and possible polypoidal choroidal vasculopathy. After completion of three injections in 147 eyes, visual acuity significantly improved, gaining ≥1 line in 51.8% of eyes and stabilising in 38.3% of 141 eyes in which visual acuity was measured. The 114 eyes approved with only one application had a better visual outcome than the 27 eyes approved after the second or third applications. In conclusion, ranibizumab is effective for nAMD; however, approval after the second or third application for national health insurance cover is a less favourable predictor of visual outcome.

Orbital complications of paranasal sinusitis in Taiwan, 1988 through 2015: Acute ophthalmological manifestations, diagnosis, and management.

PURPOSE: Paranasal sinusitis is widespread and can lead to orbital complications, blindness, and death. However, the correlation between ophthalmological findings and disease staging remains unclear. This study aimed to investigate the staging, acute ophthalmological manifestations, diagnosis, management, and outcomes of orbital complications of paranasal sinusitis during a 27-year period. METHODS: We retrospectively reviewed the medical records of all patients with orbital complications of paranasal sinusitis hospitalized at the National Cheng Kung University Hospital, a medical center in Taiwan during 1988-2015. Sex, age, symptoms, history, ophthalmological findings, laboratory and imaging findings, treatments, and outcomes were analyzed by staging. RESULTS: Eighty-three patients aged 9 days to 80 years had stage I (preseptal cellulitis, n = 39 patients), II (postseptal orbital cellulitis, n = 8), III (subperiosteal abscess, n = 16), IV (orbital abscess, n = 8), or V (intracranial involvement, n = 12) complications. Peak incidences occurred in patients aged 0-19 and 60-69 years. Chronic sinusitis and diabetes mellitus were common preexisting diseases. Extraocular movement limitation and proptosis predicted postseptal (stage II or more) involvement. The likelihood of elevated intraocular pressure increased with stage. Reduced visual acuity and presence of relative afferent pupillary defect indicated consideration of magnetic resonance imaging to investigate possible intracranial extension. Ipsilateral maxillary (81.7%) and ethmoidal (75.6%) sinuses were the most common sources of infection, and the most frequently implicated pathogens were coagulase-negative Staphylococcus spp. (25.3%) and Staphylococcus aureus (20.5%). All patients received intravenous antimicrobial therapy (multi-drug therapy in 88.0%), and 55.4% underwent surgery, most commonly endoscopic sinus surgery. One (1.2%) diabetic man with stage V complications died of fungal sinusitis with intracranial invasion. Five (6.0%) patients, all stage V, lost vision despite intensive treatment. The average length of hospital stay was 13.8 days (range 2-72 days), and significantly longer stays were associated with stages II-V as compared to stage I. CONCLUSIONS: Orbital infection originating from paranasal sinusitis can cause vision loss and death due to intracranial extension. Acute ophthalmological findings predict staging and prognosis. Cooperative consultation between ophthalmologists, otorhinolaryngologists, and neurologists is essential. Urgent diagnostic studies and aggressive antimicrobial therapy are indicated, and surgery should be considered.

Honokiol, a potential therapeutic agent, induces cell cycle arrest and program cell death in vitro and in vivo in human thyroid cancer cells.

Thyroid cancer is the most common endocrine malignancy, the global incidence rate of which is rapidly rising. Surgery and radioiodine therapies are common and effective treatments only for nonmetastasized primary tumors. Therefore, effective treatment modalities are imperative for patients with radioiodine-resistant thyroid cancer. Honokiol, a biophenolic compound derived from Magnolia spp., has been shown have diverse biological and pharmacological activities, including anti-inflammatory, antioxidative, antiangiogenic, and anticancer properties. In the present study, three human thyroid cancer cell lines, namely anaplastic, follicular, and poorly differentiated thyroid cancer cells, were used to evaluate the chemotherapeutic activity of honokiol. Cell viability, cell cycle, apoptosis, and autophagy induction were determined through flow cytometry and western blot analysis. We found that honokiol treatment can suppress cell growth, induce cell cycle arrest, and enhance the induction of caspase-dependent apoptosis and autophagy in cancer cells. Moreover, honokiol treatment modulated signaling pathways including Akt/mTOR, ERK, JNK, and p38 in the studied cells. In addition, the antitumorigenic activity of honokiol was also confirmed in vitro and in vivo. Our data provide evidence that honokiol has a unique application in chemotherapy for human thyroid cancers.

A comparative, retrospective, observational study of the clinical and microbiological profiles of post-penetrating keratoplasty keratitis.

Infectious keratitis after penetrating keratoplasty (PK) is a devastating condition that may result in graft failure and poor visual outcome. In this study, we retrospectively reviewed the medical records of patients who underwent PK between 2009 and 2014, and recorded those who developed infectious keratitis. We compared the predisposing factors and organisms isolated to those identified in our previous study, conducted between 1989 and 1994. The incidence of post-PK infectious keratitis decreased from 11.6% (41 out of 354 cases, 1989-1994) to 6.5% (9 out of 138 cases, 2009-2014). Graft epithelial defect and suture-related problems remained the leading two risk factors of infectious keratitis after PK. Gram-positive and Gram-negative bacterial infection decreased from 58.5% and 46.3% to 11.1% and 22.2%, respectively (P = 0.023 and P = 0.271). In contrast, fungus infection increased from 9.8% to 66.7% (P = 0.001); fungi have become the major pathogen for post-PK infectious keratitis. In conclusion, while the incidence of post-PK infectious keratitis has decreased over time, the number and frequency of fungal infections have significantly increased in the recent study period. Clinicians should be aware of the shifting trend in pathogens involved in post-PK infectious keratitis.

Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy.

PURPOSE: The aryl hydrocarbon receptor (AHR) is a ligand-activated nuclear receptor that regulates cellular response to environmental signals, including UV and blue wavelength light. This study was undertaken to elucidate AHR function in retinal homeostasis. METHODS: RNA-seq data sets were examined for Ahr expression in the mouse retina and rod photoreceptors. The Ahr(-/-) mice were evaluated by fundus imaging, optical coherence tomography, histology, immunohistochemistry, and ERG. For light damage experiments, adult mice were exposed to 14,000 to 15,000 lux of diffuse white light for 2 hours. RESULTS: In mouse retina, Ahr transcripts were upregulated during development, with continued increase in aging rod photoreceptors. Fundus examination of 3-month-old Ahr(-/-) mice revealed subretinal autofluorescent spots, which increased in number with age and following acute light exposure. Ahr(-/-) retina also showed subretinal microglia accumulation that correlated with autofluorescence changes, RPE abnormalities, and reactivity against immunoglobulin, complement factor H, and glial fibrillary acidic protein. Functionally, Ahr(-/-) mice displayed reduced ERG c-wave amplitudes. CONCLUSIONS: The Ahr(-/-) mice exhibited subretinal accumulation of microglia and focal RPE atrophy, phenotypes observed in AMD. Together with a recently published report on another Ahr(-/-) mouse model, our study suggests that AHR has a protective role in the retina as an environmental stress sensor. As such, its altered function may contribute to human AMD progression and provide a target for pharmacological intervention.

Retinopathy of prematurity in southern Taiwan: a 10-year tertiary medical center study.

BACKGROUND/PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. This retrospective study investigated ROP, including incidence, demographic information,risk factors, treatments, and refractive outcomes, in southern Taiwan over a 10-year period. METHODS: The authors retrieved the National Cheng Kung University Hospital database between the years 2000 and 2009 for newborns with a gestational age less than 32 weeks and/or with a birth weight less than 1500 g who had been screened for ROP. We recorded sex, birth weight, gestational age, in-hospital versus out-of-hospital birth, paternal and maternal ages, whether there were multiple gestations, parity, Apgar scores, length of hospital stay, risk factors, presence and severity of ROP and whether it was treated, and refraction at the last visit. Regression analyses were performed to identify risk factors for ROP. RESULTS: A total of 503 live births were included. ROP was identified in 190 (37.8%) and met criteria for treatment in 59 (11.7%).ROP was diagnosed as stage 1, 2, 3, 4, and 5 in 61 (12.1%), 36 (7.2%), 81 (16.1%), 11 (2.2%), and 1 (0.2%) infant, respectively. Lower birth weight and younger gestational age were risk factors for greater severity of ROP (p < 0.001). Of the 167 with extremely low birth weight (<1000 g), 118 (70.7%) had ROP and 49 (29.3%) required treatment. On univariate analysis, low birth weight, younger gestational age, and risk factors such as respiratory distress syndrome, chronic lung disease, patent ductus arteriosus, surfactant usage, indomethacin usage, sepsis, upper gastrointestinal bleeding, blood transfusion, and necrotizing enterocolitis were associated with ROP. Multivariate logistic regression analysis showed that only lower birth weight was a significant and independent risk factor for ROP. Myopia (76%)and anisometropia (28%)were common in advanced ROP. CONCLUSION: Low birth weight is a major risk factor for ROP. Infants with extremely low birth weight had a higher risk of severe ROP. Common ocular sequelae of advanced ROP were myopia and anisometropia.

Anti-Bladder-Tumor Effect of Baicalein from Scutellaria baicalensis Georgi and Its Application In Vivo.

Some phytochemicals with the characteristics of cytotoxicity and/or antimetastasis have generated intense interest among the anticancer studies. In this study, a natural flavonoid baicalein was evaluated in bladder cancer in vitro and in vivo. Baicalein inhibits 5637 cell proliferation. It arrests cells in G1 phase at 100 µ M and in S phase below 75 µ M. The protein expression of cyclin B1 and cyclin D1 is reduced by baicalein. Baicalein-induced p-ERK plays a minor role in cyclin B1 reduction. Baicalein-inhibited p65NF- κ B results in reduction of cell growth. Baicalein-induced pGSK(ser9) has a little effect in increasing cyclin B1/D1 expression instead. The translation inhibitor cycloheximide blocks baicalein-reduced cyclin B1, suggesting that the reduction is caused by protein synthesis inhibition. On the other hand, neither cycloheximide nor proteasome inhibitor MG132 completely blocks baicalein-reduced cyclin D1, suggesting that baicalein reduces cyclin D1 through protein synthesis inhibition and proteasomal degradation activation. In addition, baicalein also inhibits cell invasion by inhibiting MMP-2 and MMP-9 mRNA expression and activity. In mouse orthotopic bladder tumor model, baicalein slightly reduces tumor size but with some hepatic toxicity. In summary, these results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti-bladder-tumor effect in vivo.

Developing rods transplanted into the degenerating retina of Crx-knockout mice exhibit neural activity similar to native photoreceptors.

Replacement of dysfunctional or dying photoreceptors offers a promising approach for retinal neurodegenerative diseases, including age-related macular degeneration and retinitis pigmentosa. Several studies have demonstrated the integration and differentiation of developing rod photoreceptors when transplanted in wild-type or degenerating retina; however, the physiology and function of the donor cells are not adequately defined. Here, we describe the physiological properties of developing rod photoreceptors that are tagged with green fluorescent protein (GFP) driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca(2 +) responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. These immature rods also exhibit hyperpolarization-activated current (Ih ) induced by the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. When transplanted into the subretinal space of wild-type or retinal degeneration mice, GFP-tagged developing rods can integrate into the photoreceptor outer nuclear layer in wild-type mouse retina and exhibit Ca(2 +) responses and membrane current comparable to native rod photoreceptors. A proportion of grafted rods develop rhodopsin-positive outer segment-like structures within 2 weeks after transplantation into the retina of Crx-knockout mice and produce rectifier outward current and Ih upon membrane depolarization and hyperpolarization. GFP-positive rods derived from induced pluripotent stem (iPS) cells also display similar membrane current Ih as native developing rod photoreceptors, express rod-specific phototransduction genes, and HCN-1 channels. We conclude that Nrl-promoter-driven GFP-tagged donor photoreceptors exhibit physiological characteristics of rods and that iPS cell-derived rods in vitro may provide a renewable source for cell-replacement therapy.