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Traditionally, natural killer (NK) cells are sourced from the peripheral blood of donors―a laborious and highly donor-specific process. Processes for generating NK cells from induced pluripotent stem cells (iPSCs) have demonstrated that it is possible to successfully generate renewable alloreactive NK cells that are not only functional in vivo but can also be genetically engineered for enhanced function. However, poor standardization and cumbersome differentiation procedures suggest that further improvements in the control of the differentiation process are necessary. Here the authors evaluated the potential of differentiating NK cells from centrally authenticated iPSCs under entirely chemically defined and serum-free conditions as well as their immunotherapeutic potential, after expansion in feeder-free media, against solid tumors targets. To address limitations of current differentiation approaches, the authors did not utilize feeder or stromal cell layers, TrypLE adaptation or peripheral blood during the differentiation process. The authors also evaluated the feasibility of utilizing centrally authenticated iPSC lines, thus circumventing protocol- and donor-induced variability associated with reprogramming approaches, and characterized these iPSC-NK cells in terms of cytotoxicity, cytokine production and degranulation potential against solid tumor cell lines and patient-derived targets. Differentiation of iPSCs generated NK cells that were predominantly CD56+/CD16+/CD3− and expressed NK activation markers NKG2D, NKp30, NKp44, NKp46 and DNAM-1. These iPSC-NK cells mediated effector functions, including cytotoxicity, degranulation and IFN-γ production, in response to solid tumor targets, including patient-derived cancer cells, and could be cryopreserved and expanded in culture. The ability to produce NK cells under defined conditions and the functional responses elicited by these iPSC-NK cells suggest that they could represent promising effectors in clinical adoptive transfer settings as a renewable source of donor-independent NK cells for immunotherapy of solid tumors. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association between the presence and severity of migraine and development of primary open-angle glaucoma (POAG) using a nationwide population-based longitudinal cohort data. Methods: Data were retrieved from the Korean National Health Insurance Service for 2,716,562 individuals aged ≥ 40 years and assessed for the development of POAG from 2009 through 2018. Subjects were classified into the following 3 groups: healthy control subjects, subjects with mild migraine, and those with severe migraine. Hazard ratios (HR) of glaucoma development were calculated for each group. Subgroup analyses of subjects stratified by age, sex, lifestyle factors (smoking, drinking, and body mass index (BMI)), and comorbidities (diabetes, hypertension, and dyslipidemia). Results: During the 9-year follow-up period, the incidence rate of POAG per 1000 person-years was 2.41 and 3.25 in subjects without and with migraine, respectively. Among the migraine group, the incidence rate was 3.14 and 3.89 in mild and severe subgroups, respectively. The HR was 1.355 (95% CI, 1.300–1.412) and 1.188 (95% CI, 1.140–1.239) before and after adjusting for potential confounding factors in the migraine group per se. Regarding the severity of migraine, the adjusted HRs were 1.169 (95% CI, 1.117–1.224) in the mild migraine group, and 1.285 (95% CI, 1.166–1.415) in the severe migraine group compared to the control group. The results were consistent in subgroup analyses after stratifying by age, sex, lifestyle factors, and comorbidities. Conclusions: Migraine is associated with increased risk of POAG development. Furthermore, chronic and severe migraine is associated with greater risk of POAG development. [ABSTRACT FROM AUTHOR]

Abstract: Target-derived factors modulate many aspects of peripheral neuron development including neuronal growth, survival, and maturation. Less is known about how initial target contact regulates changes in gene expression associated with these developmental processes. One early consequence of contact between growing sympathetic neurons and their cardiac myocyte targets is the inhibition of neuronal outgrowth. Analysis of neuronal gene expression following this contact revealed coordinate regulation of a bone morphogenetic protein (BMP)-dependent growth pathway in which basic helix–loop–helix transcription factors and downstream neurofilament expression contribute to the growth dynamics of developing sympathetic neurons. BMP2 had dose-dependent growth-promoting effects on sympathetic neurons cultured in the absence, but not the presence, of myocyte targets, suggesting that target contact alters neuronal responses to BMP signaling. Target contact also induced the expression of matrix Gla protein (MGP), a regulator of BMP function in the vascular system. Increased MGP expression inhibited BMP-dependent neuronal growth and MGP expression increased in sympathetic neurons during the period of target contact in vivo. These experiments establish MGP as a novel regulator of BMP function in the nervous system, and define developmental transitions in BMP responses during sympathetic development. [Copyright &y& Elsevier]

This study investigated the potential associations between allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) and the development of primary open-angle glaucoma. We utilized authorized data from the Korean National Health Information Database (KNHID), which provides comprehensive medical claims data and information from the National Health Screening Program. We compared the baseline characteristics of subjects with and without allergic diseases and calculated the incidence and risk of glaucoma development. Cox proportional hazard regression analysis was used to determine the risk of glaucoma development in subjects with allergic diseases. A total of 171,129 subjects aged 20–39 with or without allergic diseases who underwent a general health examination between 2009 and 2015 were included. Subjects with allergic diseases exhibited a higher incidence of glaucoma compared to the control group. The hazard ratio (HR) of glaucoma onset was 1.49 and 1.39 in subjects with at least one allergic disease before and after adjusting for potential confounding factors, respectively. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development (aHR 1.73) after adjusting for confounders. Allergic rhinitis showed an increased risk for incident glaucoma after adjustment (aHR 1.38). Asthma showed the lowest but still increased risk for glaucoma (aHR 1.22). The associations were consistent in all subgroup analyses stratified by sex, smoking, drinking, exercise, diabetes, hypertension, dyslipidemia, or history of steroid. In conclusion, allergic diseases are associated with increased risk of glaucoma development. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development followed by allergic rhinitis and asthma. [ABSTRACT FROM AUTHOR]

Aims/Purpose: To investigate the association between metabolic syndrome and localized retinal nerve fibre layer (RNFL) defects in nonglaucomatous subjects. Methods: We examined 20 385 adults at the Health Promotion Center in Seoul St. Mary's Hospital between May 2015 and April 2016. Subjects with and without localized RNFL defects were 1:5 propensity score matched. Metabolic syndrome components, central obesity, elevated triglyceride, reduced HDL cholesterol, elevated blood pressure and elevated fasting glucose, were compared between two groups. Logistic regression was performed to investigate the association between RNFL defects and each metabolic syndrome component as well as the number of metabolic syndrome components. Results: Subjects with RNFL defects showed higher waist to hip ratio, systolic and diastolic BP, fasting blood glucose and HbA1c compared to those without RNFL defects before and after propensity score matching. The number of metabolic syndrome components was significantly greater in those with RNFL defects (1.66 ± 1.35) compared to those without (1.27 ± 1.32, p < 0.01). In multivariate logistic regression, the odds of RNFL defects were significantly increased in subjects with central obesity (OR = 1.53, 95% confidence interval [CI] = 1.11–2.13), elevated blood pressure (OR = 1.50, 95% CI = 1.09–2.05), and elevated fasting glucose (OR = 1.42, 95% CI = 1.03–1.97). Greater number of metabolic syndrome components was associated with higher odds of RNFL defects. Conclusions: The presence of localized RNFL defects in nonglaucomatous subjects is associated with metabolic syndrome components, including central obesity, elevated BP and elevated fasting glucose, suggesting that comorbid metabolic syndromes should be considered when evaluating subjects with RNFL defects. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between corneal deflection amplitude and visual field progression rate in patients with primary open-angle glaucoma (POAG). Methods: This study included 113 eyes of 65 patients with POAG followed for an average of 4.81 ± 1.24 years. Evaluation of visual field progression rate was performed using mean deviation of standard automated perimetry. Corneal deflection amplitude was measured using Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany). Linear mixed models were performed to determine the relationship between corneal deflection amplitude, intraocular pressure (IOP), and visual field progression rate. Results: Mean age was 56.36 ± 14.58 years. Baseline average mean deviation was -8.20 ± 9.12 dB and mean treated IOP was 14.38 ± 3.08 mmHg. Average deflection amplitude was 0.90 ± 0.13 mm. In both univariate and multivariate analysis, IOP (P = 0.028 and P < 0.001, respectively) and deflection amplitude (P = 0.034 and P < 0.001, respectively) significantly affected visual field progression rate. Eyes with high IOP and greater deflection amplitude showed faster progression rate. Conclusions: Corneal deflection amplitude was significantly related with glaucoma progression. Eyes with greater corneal deflection amplitude showed faster visual field progression rate in patients with POAG. [ABSTRACT FROM AUTHOR]

Obesity has been associated with increased intraocular pressure (IOP), but the results are inconsistent. Recently, a subgroup of obese individuals with good metabolic profiles were suggested to have better clinical outcomes than normal-weight individuals with metabolic diseases. The relationships between IOP and different combinations of obesity and metabolic health status have not been investigated. Therefore, we investigated the IOP among groups with different combinations of obesity status and metabolic health status. We examined 20,385 adults aged 19 to 85 years at the Health Promotion Center of Seoul St. Mary's Hospital between May 2015 and April 2016. Individuals were categorized into four groups according to obesity (body mass index (BMI) ≥ 25 kg/m2) and metabolic health status (defined based on prior medical history or abdominal obesity, dyslipidemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting blood glucose levels upon medical examination). ANOVA and ANCOVA were performed to compare the IOP among the subgroups. The IOP of the metabolically unhealthy obese group (14.38 ± 0.06 mmHg) was the highest, followed by that of the metabolically unhealthy normal-weight group (MUNW, 14.22 ± 0.08 mmHg), then, the metabolically healthy groups (p < 0.001; 13.50 ± 0.05 mmHg and 13.06 ± 0.03 mmHg in the metabolically healthy obese (MHO) and metabolically healthy normal-weight groups, respectively). Subjects who were metabolically unhealthy showed higher IOP compared to their counterparts who were metabolically healthy at all BMI levels, and there was a linear increase in IOP as the number of metabolic disease components increased, but no difference between normal-weight vs. obese individuals. While obesity, metabolic health status, and each component of metabolic disease were associated with higher IOP, those who were MUNW showed higher IOP than those who were MHO, which indicates that metabolic status has a greater impact than obesity on IOP. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The purpose of this study was to investigate the impact of vision and hearing impairments on the risk of adverse cardiovascular outcomes and mortality in patients with type 2 diabetes using a nationwide longitudinal cohort. Materials and Methods: We enrolled 771,128 patients with type 2 diabetes who underwent the National Health Screening Program in 2009. We carried out Cox proportional hazards regression analyses to calculate the hazard ratios (HR) of myocardial infarction (MI), stroke, and mortality in those with or without vision and hearing impairments. Subgroup analyses of patients stratified by age, sex and diabetic retinopathy were carried out. Results: Diabetes patients with either vision or hearing impairment showed higher risk of MI, stroke or death compared with those without. Among the combinations of impairments, patients with both vision and hearing impairments had the highest risk for MI (adjusted HR [aHR] 1.362, 95% confidence interval [CI] 1.252–1.481) and mortality (aHR 1.591, 95% CI 1.532–1.651). Those with only vision impairment showed higher risk of MI (aHR 1.324, 95% CI 1.275–1.375 and aHR 1.117, 95% CI 1.066–1.170, respectively), stroke (aHR 1.318, 95% CI 1.276–1.362 and aHR 1.134 95% CI 1.089–1.180, respectively) and mortality (aHR 1.417, 95% CI 1.390–1.446 and aHR 1.163, 95% CI 1.135–1.191, respectively) compared with those with only hearing impairment. Conclusions: Vision and hearing impairments are independently important risk factors for adverse cardiovascular events and mortality in patients with type 2 diabetes. Vision and hearing impairments synergistically increased the risk of MI and all‐cause deaths, but not stroke. In addition, in patients aged <65 years, the HR of vision impairment was higher than those with vision and hearing impairments. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of topical application of cyclosporine or vitamin A on the ocular surface during the concurrent administration of antiglaucoma drugs. Methods: Thirty rabbits were randomized into 5 groups. Group 1 was administered timolol, group 2 received travoprost, group 3 received a travoprost/timolol fixed combination solution, group 4 received timolol and travoprost, and group 5 received timolol, travoprost, and dorzolamide. Each group was divided into a subgroup that received only the antiglaucoma medication (subgroup A), a subgroup that received topical cyclosporine in addition to the antiglaucoma medication (subgroup B), and a subgroup that received topical vitamin A in addition to the antiglaucoma medication (subgroup C). Conjunctival impression cytology specimens were collected at baseline and at weeks 1, 3, and 6. Conjunctival biopsy specimens were collected at week 6. Results: The impression cytologic study results are as follows: statistically significant differences were found between groups 4A and 4B and between groups 4A and 4C at week 6 (p = 0.004, p = 0.006, respectively) and between groups 5A and 5B and between groups 5A and 5C at weeks 3 and 6 (p = 0.006, p = 0.008 at week 3, p = 0.003, p = 0.004 at week 6, respectively). No statistically significant differences were found between subgroup B and subgroup C in any of the groups at any of the times evaluated (p > 0.05). The conjunctival biopsy specimens from groups 1, 2, and 3 showed no distortion, but groups 4A and 5A showed distortion of the conjunctival epithelial structures. Groups 4B, 4C, 5B, and 5C showed less distortion of the conjunctival epithelial structures. Conclusion: Administration of cyclosporine or vitamin A may reduce the adverse ocular surface changes caused by long-term administration of antiglaucoma drugs. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

• Clinically-compatible advances in EPC isolation and reprogramming. • Reduced blood-sampling volumes from 80 mL to 10 mL allowing wider use of EPCs. • Unlike other blood-derived cells, EPCs can be reprogrammed with RNA. • EPC-RNA-iPSCs maybe clinically translatable, carrying minimal chromosomal changes. The promise of using induced pluripotent stem cells (iPSCs) for cellular therapies has been hampered by the lack of easily isolatable and well characterized source cells whose genomes have undergone minimal changes during their processing. Blood-derived late-outgrowth endothelial progenitor cells (EPCs) are used for disease modeling and have potential therapeutic uses including cell transplantation and the translation of induced pluripotent stem cell (iPSC) derivatives. However, the current isolation of EPCs has been inconsistent and requires at least 40−80 mL of blood, limiting their wider use. In addition, previous EPC reprogramming methods precluded the translation of EPC-derived iPSCs to the clinic. Here a series of clinically-compatible advances in the isolation and reprogramming of EPCs is presented, including a reduction of blood sampling volumes to 10 mL and use of highly efficient RNA-based reprogramming methods together with autologous human serum, resulting in clinically relevant iPSCs carrying minimal copy number variations (CNVs) compared to their parent line. [ABSTRACT FROM AUTHOR]

Although depression and glaucoma share several common pathophysiology, the risk of glaucoma in patients with depression has not been reported. Thus, we investigated the effect of depressive symptom and depressive disorder on glaucoma incidence. In this nationwide population-based cohort study, all subjects receiving the National Screening Program at the age of 66 during 2009–2014 were included. These subjects were divided into depression group and no depression group based on subjective depressive symptoms and clinically diagnosed depressive disorder and were tracked until 2017 for development of glaucoma. Of the 922,769 subjects included in the study, 191,636 (20.77%) subjects were categorized as depression group. Subjects with depression showed increased hazard of developing glaucoma (adjusted HR = 1.12[95% confidence interval (CI), 1.09–1.15]) than those without depression. The risk of glaucoma increased sequentially from those with no depression to those with subjective depressive symptom (adjusted HR = 1.09[95% CI, 1.06–1.13]), those with clinically diagnosed depressive disorder (adjusted HR = 1.23[95% CI, 1.14–1.32]), and those with both subjective depressive symptom and clinically diagnosed depressive disorder (adjusted HR = 1.36[95% CI, 1.22–1.52]). Our analyses suggest that individuals with depression had a greater risk of developing glaucoma than those without depression. Subjective depressive symptoms and clinically diagnosed depressive disorder independently and synergistically increased the risk of glaucoma incidence. [ABSTRACT FROM AUTHOR]

To compare the risk of cancer development between patients with glaucoma and those without, we conducted a nationwide population-based cohort study using the Korean National Health Insurance Database. Individuals with diagnosis of glaucoma between 2007 and 2016 were identified, and controls were 1:1 matched based on age and sex. We calculated the incidence rates(IR) and hazard ratios(HR) before and after adjusting for age, gender, diabetes, smoking history, and body mass index. A total of 107,536 individuals with glaucoma and the same number of individuals without glaucoma were included. The IR of overall cancer were 12.23 and 11.62 per 1,000 individuals in the glaucoma and control groups, respectively. The HR of overall cancer was significantly higher in the glaucoma group before(HR: 1.053) and after adjusting for confounding factors(adjusted HR: 1.049) compared to that in the control group. The risk of overall cancer and specific cancers varied depending on gender and age groups, and the association was stronger in women and those under 65 years of age. Our study revealed that individuals with glaucoma showed higher risk of overall cancer and higher risk of specific cancers than those without glaucoma. [ABSTRACT FROM AUTHOR]

mRNA reprogramming results in the generation of genetically stable induced pluripotent stem (iPS) cells while avoiding the risks of genomic integration. Previously published mRNA reprogramming protocols have proven to be inconsistent and time-consuming and mainly restricted to fibroblasts, thereby demonstrating the need for a simple but reproducible protocol applicable to various cell types. So far there have been no published reports using mRNA to reprogram any cell type derived from human blood. Nonmodified synthetic mRNAs are immunogenic and activate cellular defense mechanisms, which can lead to cell death and inhibit mRNA translation upon repetitive transfection. Hence, to overcome RNA-related toxicity we combined nonmodified reprogramming mRNAs (OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 [OSKMNL]) with immune evasion mRNAs (E3, K3, and B18R [EKB]) from vaccinia virus. Additionally, we included mature, double-stranded microRNAs (miRNAs) from the 302/367 cluster, which are known to enhance the reprogramming process, to develop a robust reprogramming protocol for the generation of stable iPS cell lines from both human fibroblasts and human blood-outgrowth endothelial progenitor cells (EPCs). Our novel combination of RNAs enables the cell to tolerate repetitive transfections for the generation of stable iPS cell colonies from human fibroblasts within 11 days while requiring only four transfections. Moreover, our method resulted in the first known mRNA-vectored reprogramming of human blood-derived EPCs within 10 days while requiring only eight daily transfections. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) plays a critical role in cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH decrease using [D, L]-buthionine sulphoximine (BSO) induces retinal cell death, but the underlying mechanisms of this are still unclear. Here, we demonstrated that retinal GSH level is closely related to retinal cell death as well as expression of an anti-apoptotic molecule, Bcl-2, in the retina. We induced differential expression of retinal GSH by single and multiple administrations of BSO, and examined retinal GSH levels and retinal cell death in vivo. Single BSO administration showed a transient decrease in the retinal GSH level, whereas multiple BSO administration showed a persistent decrease in the retinal GSH level. Retinal cell death also showed similar patterns: transient increases of retinal cell death were observed after single BSO administration, whereas persistent increases of retinal cell death were observed after multiple BSO administration. Changes in the retinal GSH level affected Bcl-2 expression in the retina. Immunoblot and immunohistochemical analyses showed that single and multiple administration of BSO induced differential expressions of Bcl-2 in the retina. Taken together, the results of our study suggest that the retinal GSH is important for the survival of retinal cells, and retinal GSH appears to be deeply related to Bcl-2 expression in the retina. Thus, alteration of Bcl-2 expression may provide a therapeutic tool for retinal degenerative diseases caused by retinal oxidative stress such as glaucoma or retinopathy. [ABSTRACT FROM AUTHOR]

It is known that in advanced hypertensive retinopathy, which changes advanced hypertensive retinopathy (Grade III or IV), there is a strong relation between retinal microvascular lesions and cardiac and macrovascular markers of target organ damage (TOD). The prevalence of grade II hypertensive retinopathy and its relationship to cardiovascular risk factors remain controversial. The subjects, a total of 437 hypertensive patients, were divided into three groups according to modified Keith, Wagener, and Barker (KWB) classification by two ophthalmologists: Grade 0 with normal retinal change (N = 169, 38.7%), Grade I with arteriolar narrowing (N = 215, 49.1%), Grade II with arteriovenous crossings (N = 49, 11.2%). The prevalence of Grade I and Grade II hypertensive retinopathy was significantly higher than that of advanced hypertensive retinopathy. The grade of hypertensive retinopathy was related to age, duration of hypertension, coronary artery disease (CAD), and left ventricular hypertrophy (LVH). The prevalence of LVH and CAD in Grade II was significantly higher than in Grade I and Grade 0. The hypertensive retinopathy Grade II was significantly correlated with LVH (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.21-4.44, p < 0.05) and CAD (OR 4.2, 95% CI 1.97-8.95, p-<-0.001). Grade I and Grade II hypertensive retinopathy are frequently observed in hypertensive patients compared to Grade III and IV patients. We concluded that Grade II hypertensive retinopathy is closely related to CAD and should therefore not be ignored. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative stress affects numerous intracellular macromolecules, and may result in cell death unless precisely regulated. Unregulated oxidative stress can be controlled by various cellular defense mechanisms such as glutathione (GSH) which can critically counteract the damaging effects of oxidative stress in mammalian cells. We determined the effects of unregulated oxidative stress induced by GSH depletion on cells in mouse retina. Mice were intraperitoneally injected with buthionine sulphoximine (BSO) at 1.5g/kg. After 0, 1, 4, and 7 days of BSO administration, retinas were excised and sections were subjected to GSH assay and terminal uridine deoxynucleotidyl nick end labeling (TUNEL) analysis. After 4 days of BSO administration, the number of TUNEL positive cells was significantly increased. However, after 7 days, TUNEL positive cells returned to the basal level. The retinal region most affected by the BSO treatment appeared to be the outer nuclear layer where the photoreceptor cells reside. Different from cells in other regions, retinal cells in the inner nuclear layer increased in their apoptosis even after the first day of BSO injection, and the increase was further potentiated after 4 days. Taken together, our studies suggested that GSH depletion may cause unregulated oxidative stress to the cells in the retina and indeed increased cell death in the retina. The cells in the inner nuclear layer seemed to be affected earlier than the cells in other layers of the retina. The GSH level in the retina may be a crucial therapeutic target in preventing blindness. [Copyright &y& Elsevier]

Abstract: Heat shock proteins (HSPs) are highly conserved proteins playing a protective role under deleterious conditions caused by a wide variety of pathophysiological, including environmental stresses. Glutathione (GSH) is known to play a critical role in the cellular defense against unregulated oxidative stress in mammalian cells including neurons. We previously demonstrated that GSH depletion induced cell death in the retina, but the mechanism(s) of cellular protection were not clear. Unregulated oxidative stress was induced by depletion of intracellular GSH by systematic administration of buthionine sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase. After 0, 1, 4 and 7 days of BSO administration, we examined expression of both large and small HSP mRNAs (hsp90α, hsp90β, hsp70, hsp60 and hsp25) in oxidative-stressed mouse retina. Of large HSPs, only hsp70 expression was significantly decreased from 1 day after BSO injection, whereas expression of other large hsps was not changed on day 1. Expression of hsp60 decreased on 4 days, whereas expression of hsp90 decreased on 7 days after BSO administration. Different from large HSPs, a small HSP, hsp25 increased its expression to a great extent from 1 day after BSO administration. Taken together, our results show that unregulated oxidative stress could induce differential expression of HSPs, which, in turn, may play distinct roles in the cellular defense. Targeting HSPs, therefore, may provide novel tools for treatment of retinal degenerative diseases such as glaucoma, retinopathy or age-related macular degeneration. [Copyright &y& Elsevier]

The FVB/N mouse is a model of retinitis pigmentosa which shows a rapid loss of photoreceptors during early postnatal (P) life. We investigated the cellular localization of glycine transporter 1 (GlyT-1) in the developing FVB/N mouse retina. In control retinas, the developmental pattern of GlyT-1-immunoreactive amacrine cells was well in accordance with a previous report. However, in the FVB/N mouse retina, some GlyT-1-labeled amacrine cells sent their processes into the outer plexiform layer (OPL) from P14 onward. From P21 onward, GlyT-1-labeled cells were visible in the OPL. These cells were further characterized by double-label immunofluorescence experiments with an antiserum against disabled 1 (Dab-1), and showed Dab-1 immunoreactivity, indicating that these cells are putative AII amacrine cells. These results clearly demonstrate that AII amacrine cells have the potential capacity to respond to photoreceptor degeneration by migrating or sprouting their processes into the OPL in the developing FVB/N mouse retina. [ABSTRACT FROM AUTHOR]

This study investigated the expression and cellular localization of neuronal nitric oxide synthase in the rat retina following optic nerve transection (ONT). In the normal rat retina, nNOS immunoreactivity was localized to amacrine cells and displaced amacrine cells. A few bipolar cells were also labeled. In the axotomized retina, ganglion cells showed nNOS immunoreactivity from 3 days after ONT, and these cells increased in number, peaking 5 days after ONT. Quantitative evaluation using immunoblotting confirmed that nNOS expression showed a peak value (255% of control levels) 5 days after ONT and decreased to 137% of controls by 28 days. These findings suggest that axotomized ganglion cells degenerate via NO-mediated excitotoxicity. [Copyright &y& Elsevier]