Published papers

Purpose To assess the effect of laser in situ keratomileusis (LASIK) on near visual function in presbyopic patients. Design Retrospective cohort study. Methods Fifty-three eyes of 40 patients 45 years of age and older who had undergone LASIK for high myopia (-6 diopters [D] and over) were included. The minimal add powers for obtaining the best-corrected near visual acuity (add powers) were measured preoperatively and 3 months postoperatively, and the correlations with the powers corrected by LASIK, corneal higher-order aberrations (HOAs), ocular HOAs, and patient ages were evaluated using univariate analysis. Factors correlated with the changes in add powers were evaluated further by multivariate analysis. Results The mean ± standard deviation patient age was 50.0 ± 4.1 years; the power corrected by LASIK was -7.56 ± 1.06 D. The mean add power was 1.80 ± 0.60 D preoperatively, which increased significantly (P <.001) to 2.18 ± 0.69 D postoperatively. Significant correlations with the increased add powers were detected with age (P =.01) and the power corrected by LASIK (P =.04) but not with corneal and ocular HOAs (P >.05). Multivariate analysis showed that only age was correlated significantly (P =.01). The percentage of eyes with increased add powers of 0.5 D or more was 60.4%, which was significantly (P =.02) higher in younger patients. Conclusions This study verified the apparent progression of presbyopia after LASIK and the importance of obtaining informed consent from patients, especially those with early presbyopia. © 2014 by Elsevier Inc. All rights reserved.

Purpose. To investigate the effects of exercise on tear secretion in type 2 diabetic mice, and to investigate the effect of the adenosine monophosphate-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). Methods. Heterozygous controls (db/m; m Leprdb) and type 2 diabetic mice (db/db; Leprdb) either underwent forced treadmill exercise training 5 days a week or remained sedentary for 8 weeks. Tear secretion volume was measured by cotton threads for 30 seconds pre- and post intervention. The levels of oxidative stress markers (8-hydroxy-20-deoxyguanosine [8-OHdG], propanoyl lysine [PRL], and hexanoyl lysine [HEL]) in tears were measured in the postintervention period. Furthermore, C57BL/6JJc1 mice, db/db mice, and db/m mice received a single intraperitoneal injection of AICAR or PBS each day for 5 days, and tear secretion volume was measured. Results. Exercise training for 8 weeks increased tear secretion volume in db/m and db/db mice. The levels of oxidative stress markers in tears were less in the exercise group than in the control group. In C57BL/6JJc1 mice, the tear secretion volumes in both the AICAR 125 mg/kg and AICAR 250 mg/kg groups were significantly larger than in the PBS group (P < 0.01 and P < 0.01, respectively). Additionally, in db/db mice, tear secretion volume in the AICAR 125 mg/kg group was also significantly larger than in the PBS group (P < 0.05). Conclusions. Exercise training for 8 weeks and a daily injection of AICAR for 5 days increased tear secretion in mice. The results suggest that exercise may be a potential therapy to modulate tear secretion. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

Purpose: To investigate the differences of functional visual acuity (FVA) and high order aberrations (HOAs) in relation to tinted and clear hydrogel soft contact lens (SCL) wear. Methods: A prospective comparative study was performed in 16 eyes of 16 healthy volunteers. Dynamic visual acuity (using a FVA measurement system) and higher-order aberrations (using a wavefront sensor) were compared in subjects wearing two types of soft contact lenses: 1-day Acuvue® (Vistakon, Jacksonville, FL) clear and the 1-day Acuvue® DefineTM (Vistakon, Jacksonville, FL) tinted lens. The blink rates were recorded during FVA testing. The correlation between the difference of HOAs and differences in FVA values was analyzed. Results: The mean LogMAR FVA scores with clear and tinted SCLs were 0.07 ± 0.13 and 0.14 ± 0.17 (P< 0.05). The mean blink frequencies with clear and tinted SCL wear were 18.4 ± 8.3 and 25.3 ± 4.7. blinks/min (P< 0.05). Both 3rd-order aberrations and total HOAs showed statistically significant differences between the two types of soft contact lenses for 6. mm pupil measurements (P< 0.05). A significant positive linear correlation was observed between δHOAs and δLogMAR FVA for 6. mm pupil measurements (R= 0.53, P= 0.04). Conclusions: Tinted contact lens wear appears to induce a reduction in optical quality. Functional visual acuity measurement is a useful procedure to study the changes of visual performance and quality in tinted contact lens wear. © 2013 British Contact Lens Association.

Purpose: To investigate the relationship between visual field (VF) damage and history of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods: MVC history and driving habits were recorded using patient questionnaires in 247 POAG patients. Patients' driving attitudes (carefulness) were estimated using Rasch analysis. The relationship between MVC outcomes and 52 total deviation (TD) values of integrated binocular VF (IVF), better and worse visual acuities (VAs), age and gender was analyzed using principal component analysis and logistic regression. Results: 51 patients had the history of MVCs. Significant difference was observed between patients with and without history of MVCs only for: better VA, a single TD value in the superior-right VF, and the typical distance driven in a week (unpaired t-test, p=0.002, 0.015 and 0.006, respectively). There was not a significant relationship between MVCs and mean deviation (MD) of IVF (p=0.41, logistic regression). None of the principal components were significantly correlated with MVC outcome (p>0.05, polynomial logistic regression analysis). There was a significant relationship between IVF MD and Rasch derived Person parameter (R2=0.023, p=0.0095). There was also a significant positive relationship between MVCs and the distance driven in a week (p=0.005, logistic regression). Conclusions: In this study of POAG patients, MVCs were not related to central binocular VF damage. These results suggest the relationship between visual function and driving is not straightforward, and careful consideration should be given when predicting patients' driving ability using their VF.

The development of choroidal neovascularization (CNV) is a critical step in the pathogenesis of age-related macular degeneration (AMD), a vision-threatening disease. In this study, we used a mouse model of AMD to study the protective effects of resveratrol (RSV) supplementation against CNV as well as the underlying molecular mechanisms. Mice were orally pretreated with RSV daily for 5. days. On the fifth day, the mice underwent laser photocoagulation to induce CNV. One week after laser treatment, CNV volume was significantly lower in the RSV-treated mice compared with vehicle-treated animals. In addition, RSV treatment significantly inhibited macrophage infiltration into the retinal pigment epithelium (RPE)-choroid and suppressed the expression of inflammatory and angiogenic molecules, including vascular endothelial growth factor, monocyte chemotactic protein-1 and intercellular adhesion molecule-1. Importantly, RSV prevented the CNV-induced decrease in activated AMP-activated protein kinase and increase in activated nuclear factor-κB in the RPE-choroid complex. The regulatory effects of RSV on these molecules were confirmed in RPE, microvascular endothelial and macrophage cell lines. Inhibition of macrophage infiltration by RSV was confirmed by in vitro scratch and migration assays. RSV suppressed CNV development, reducing the levels of multiple cytokines secreted from several cell types and inhibiting macrophage migration. The direct effects of RSV on each cell type were confirmed in vitro. Although further studies are needed, RSV could potentially be applied in the clinic to prevent CNV development in AMD.

Recent advances in ocular surface reconstruction for patients with severe ocular surface diseases have significantly improved the prognosis of patients with vision-impairing corneal abnormalities. The history of cultivated epithelial sheet transplantation is short, and debate on the current approaches for these procedures is continuing. Limbal stem cell transplantation, including conjunctivolimbal autograft and keratolimbal allograft, has brought opportunities for vision improvement. In addition, the use of cultivated limbal epithelial transplantation from both allogeneic and autologous sources has provided further options for immediate postoperative epithelialization of the corneal surface. Finally, cultivated oral mucosal epithelial transplantation, which allows autologous transplantation for patients with bilateral limbal stem cell deficiency, has provided the best overall midterm and long-term results. Its biggest advantages are the absence of rejection reactions and the reduction of postoperative complications associated with steroid therapy. However, a solitary surgical approach is not sufficient for obtaining a good clinical outcome. To maximize the possibility of success using these procedures, it is important to preoperatively enhance aggressive treatment of the ocular surface, especially with factors that facilitate moisture retention. In this review article, we also discuss our clinical experience in relation to these surgical procedures.

PURPOSE: To evaluate changes in functional visual acuity (FVA) measurements before and after treatment with 0.1% cyclosporine ophthalmic solution for 3 months in patients with severe atopic keratoconjunctivitis (AKC).METHODS: Pairs of eyes were analyzed from 3 boys (mean age 9 ± 3.6 years) who complained of having severe AKC and were recruited for the study. Conventional Landolt visual acuity, FVA, and visual maintenance ratio (VMR) measurements were conducted before and after 3 months of 0.1% cyclosporine eye drop treatment. Tear film lipid layer interferometry, tear film break-up time, fluorescein and rose bengal vital stainings, and the Schirmer test were also performed before and after treatment.RESULTS: Eye drop treatment was associated not only with improvement of tear function and ocular surface status but also with better quality of visual function. The mean logarithm of the minimum angle of resolution FVA and Landolt visual acuity values improved from 0.45 ± 0.26 and 0.13 ± 0.17 before treatment to 0.16 ± 0.03 and -0.06 ± 0.05 after treatment, respectively. Similarly, the mean VMR values were markedly improved from 0.88 ± 0.06 to 0.95 ± 0.03 after treatment.CONCLUSIONS: FVA and VMR are promising parameters in the assessment of dynamic visual acuity changes in AKC-affected patients and evaluation of treatment outcome.

PURPOSE:: To report that spontaneous postkeratoplasty wound dehiscence or gaps caused by suture removal may occur years after penetrating and deep lamellar keratoplasty.METHODS:: We retrospectively reviewed the medical records of 667 keratoplasty patients (890 eyes). This study included 8 eyes of 8 patients (3 men and 5 women) aged 64 to 86 years who suffered from spontaneous wound dehiscence or gaps caused by suture removal. We examined their clinical backgrounds such as surgical procedure, reason for suture removal, and time interval between keratoplasty and suture removal.RESULTS:: The surgical procedures included 6 penetrating keratoplasties and 2 deep anterior lamellar keratoplasties. The most common reason for suture removal was high corneal astigmatism. Time interval between keratoplasty and suture removal was 15.9 ± 7.7 months (7–26 months). Three patients underwent suture removal from 6 months to 1 year after keratoplasty, 3 patients from 1 to 2 years, and 2 patients after more than 2 years.CONCLUSIONS:: Whenever postoperative keratoplasty suture is removed, it is important to consider that wound dehiscence or gaps may occur without incidence of trauma.

Background: Macular hole results from a tractional force at the vitreo-retinal interface which is developed by modification and subsequent degeneration of the posterior precortical vitreous and the internal limiting membrane (ILM). Meanwhile, the wet type of age-related macular degeneration (AMD) is caused by the submacular formation of choroidal neovascularization (CNV). Although exudative changes derived from CNV may cause epiretinal membrane (ERM) formation, which can also cause tractional force at the vitreo-retinal interface, there have been few reports of AMD-associated macular hole development in which the full thickness of the retinal tissue is completely torn by the tractional force. Moreover, intraoperative finding of macular hole associated with AMD with a possible involvement of subretinal lesion has not been described.Case presentation. A 78-year-old man diagnosed with wet AMD with subretinal fluid and mild cataract received 8 treatments with intravitreal pegaptanib. After AMD remission, he developed a secondary macular hole in the same eye. He underwent a pars plana vitrectomy that successfully closed the macular hole. Intraoperatively, it was found that the patient's vitreous was formed and that the ERM and ILM were adherent, suggesting the involvement of a tractional force at the vitreo-retinal interface due to an inflammatory reaction related to AMD and/or intravitreally injected chemical compounds, resulting in macular hole development. Changes in the condition of his AMD and the RPE were observed on a fluorescein angiogram (FA) and an indocyanine green angiogram (IA) that preceded macular hole development, suggesting that subretinal changes may also have been involved in the pathogenesis.Conclusion: These clinical data, including the intraoperative findings and the temporal changes in the angiograms, suggest that an inflammatory reaction at the vitreo-retinal interface and subretinal lesion related to AMD contribute to the macular hole development in AMD patients treated with intravitreal injection.

Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG. Copyright:

Purpose: To report the first multicenter survey in Japan on infectious keratitis after excimer laser surgery. Methods: The laser in situ keratomileusis (LASIK) Safety Network (LSN) Committee sent questionnaires to 28 LSN member hospitals to assess the total number of laser corneal surgeries, the number of infection cases (including suspicious cases), and the postoperative follow-up rate during a 3-year period. Results: Responses were obtained from 27 (96.4%) of 28 institutions. One phototherapeutic keratectomy infection case was reported among 22,415 excimer laser surgery cases, which equates to an incidence rate of 0.004%. The follow-up rate was 94.14% (67.2-100%), 80.11% (41.0-96.1%), 57.95% (11.5-93.0%), and 46.64% (4.7-93.0%) at 1 month, 3 months, 6 months, and 12 months of follow-up, respectively. Conclusion: Infectious keratitis is a potentially devastating complication of excimer laser surgery. We did not see any infectious keratitis for refractive cases. This first multicenter survey in Japan on infectious keratitis provides important information on the safety of this therapy.

Dry eye disease is a disorder in tear film physiology, which leads to various abnormal states of ocular surface cells. In the present study, we evaluated the potential usefulness of orally applied maqui berry (. Aristotelia chilensis) extract and the constituent anthocyanin as a preventative intervention in dry eye. Tear secretion capacity was evaluated following the oral administration of maqui berry extract to a rat blink-suppressed dry eye model. This suppressive effect of maqui berry extract and its constituent anthocyanins on reactive oxygen species formation from lacrimal gland was elevated by 2', 7'-dichlorofluorescin diacetate. Maqui berry extract and delphinidin 3,5-O-diglucoside, an anthocyanin specifically contained in the maqui berry, suppressed reactive oxygen species formation from lacrimal gland tissue and preserved tear secretion. The result of the present study demonstrates that maqui berry extract can be used as a preventative intervention for dry eye by managing tear secretion capacity in the lacrimal gland.

Background: Fasting is a rigorous type of dietary restriction that is associate with a number of health benefits. During fasting, ketone bodies significantly increase in blood and become major body fuels, thereby sparing glucose. In the present study, we investigated effects of fasting on hypersensitivity. In addition, we also investigated the possible role of D-beta-hydroxybutyrate provoked by fasting in the attenuation of immediate hypersensitivity by fasting. Methods. Effects of fasting on systemic anaphylaxis were examined using rat model of toluene 2, 4-diisocyanate induced nasal allergy. In addition to food restriction, a ketogenic high-fat and low-carbohydrate diet that accelerates fatty acid oxidation and systemic instillation of D-beta-hydroxybutyrate were employed to elevate internal D-beta-hydroxybutyrate concentration. We assessed relationship between degranulation of rat peritoneal mast cells and internal D-beta-hydroxybutyrate concentration in each treatment. Changes in [Ca2+]i responses to compound 48/80 were analyzed in fura 2-loaded rat peritoneal mast cells derived from the ketogenic diet and fasting. Results: Immediate hypersensitivity reaction was significantly suppressed by fasting. A significant reduction in mast cells degranulation, induced by mast cell activator compound 48/80, was observed in rat peritoneal mast cells delivered from the 24 hours fasting treatment. In addition, mast cells delivered from a ketogenic diet and D-beta-hydroxybutyrate infusion treatment also had reduced mast cell degranulation and systemic D-beta-hydroxybutyrate concentrations were elevated to similar extent as the fasting state. The peak increase in [Ca2+]i was significantly lower in the ketogenic diet and fasting group than that in the control diet group. Conclusions: The results of the present study demonstrates that fasting suppress hypersensitivity reaction, and indicate that increased level of D-beta-hydroxybutyrate by fasting plays an important role, via the stabilization of mast cells, in suppression of hypersensitivity reaction.

Background: Previously, we reported improvements in sleep quality and gait speed after implantation of a yellow-colored, blue light-blocking intra-ocular lens (IOL). This study evaluated systemic health parameters for 7 months after cataract surgery with implantation of a clear, ultraviolet (UV)-blocking IOL. Methods: A total of consecutive 71 patients (average age 74.1 years) underwent cataract surgery with the implantation of a clear, UV-blocking IOL. Participants were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and the National Eye Institute Visual Function Questionnaire (VFQ-25) before and at 2 and 7 months after surgery. Four-meter gait speed was also determined. The metabolic parameters of serum glycated hemoglobin (HbA1c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were tested. Results: The pre-operative and post-operative (2 and 7 months after surgery) results were 66.4±16.5, 79.5±12.6, and 81.0±13.0 for VFQ-25 score, 5.7±3.5, 5.1±3.1, and 4.8±2.9 for PSQI, and 0.90±0.22, 0.91±0.22, and 0.92±0.22 meters/sec for gait speed. Significant improvements following surgery were noted in the VFQ-25 score for all cases and in the PSQI for poor sleepers (preoperative PSQI >5.5) (P<0.05, paired t-test). The gait speed and metabolic parameters showed no significant changes. Conclusions: Cataract surgery with implantation of an UV-blocking clear IOL has the potential for improving circadian rhythm and systemic health parameters. © 2014 Mary Ann Liebert, Inc.

Recent progress in molecular analysis has revealed the possible involvement of multiple inflammatory signaling pathways in pathogenesis of retinal degeneration. However, how aberrant signaling pathways cause tissue damage and dysfunction is still being elucidated. Here, we focus on 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), originally recognized as a key regulator of energy homeostasis. AMPK is also modulated in response to inflammatory signals, although its functions in inflamed tissue are obscure. We investigated the role of activated AMPK in the retinal neural damage and visual function impairment caused by inflammation. For this purpose, we used a mouse model of lipopolysaccharide-induced inflammation in the retina, and examined the effects of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). During inflammation, activated AMPK in the neural retina was decreased, but AICAR treatment prevented this change. Moreover, the electroretinogram (ERG) a-wave response, representing photoreceptor function, showed visual dysfunction in this model that was prevented by AICAR. Consistently, the model showed shortened photoreceptor outer segments (OSs) with reduced levels of rhodopsin, a visual pigment concentrated in the OSs, in a post-transcriptional manner, and these effects were also prevented by AICAR. In parallel, the level of activated NF-κB increased in the retina during inflammation, and this increase was suppressed by AICAR. Treatment with an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) preserved the rhodopsin level during inflammation, suppressing NF-κB. These findings indicated that AMPK activation by AICAR and subsequent NF-κB inhibition had a protective effect on visual function, and that AMPK activation played a neuroprotective role during retinal inflammation. © 2014 Kamoshita et al.

Purpose: The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 -/-) mouse. Methods: Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 -/- male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild-type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. Results: Corneal vital staining scores in the Sod1-/- mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1-/- mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1-/- mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1-/- mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1-/- mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1-/- mice. Conclusions: Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1-/- mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations. © 2014 Ibrahim et al.

Purpose: To describe a case series in which corneal fluorescein staining (CFS) development occurred in short break-up time (s-BUT) dry eyes after a short period during prolonged opening of the eye. Methods: The study was designed as a clinical case series. Ocular surface evaluations were performed on 13 individuals with s-BUT dry eye. Tear function examinations included Schirmer's test and BUT evaluation. Results: In all 13 cases, the BUT was short, but the tear quantity was not so bad. In all cases, CFS developed following a single eye opening, and the staining was observed at sites that showed as dark spots. In several cases, the CFS disappeared later. Conclusions: In this study, we demonstrated that CFS could develop following a single eye opening. Based on our findings, CFS is a dynamic phenomenon rather than a stable indicator of ocular surface abnormalities. Moreover, s-BUT dry eye has the potential to show ocular surface abnormalities.

To investigate the role of a water and mucin secretagogue (3% diquafosol sodium eye drops) on the tear function and conjunctival ocular surface changes in Sod1-/- in comparison to the wild-type (WT) mice. Methods: Fourteen eyes of 7 Sod1-/- male mice with C57BL/background and 14 eyes of 7 C57BL6 strain wild-type male mice were examined at 40 weeks in this study. All mice had application of 3% diquafosol ophthalmic solution six times a day for 2 weeks. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was performed before and after eye drop instillations. Aqueous tear quantity was measured with phenol red-impregnated cotton threads without anesthesia. Animals were sacrificed at 42 weeks after diquafosol treatment and the whole globe specimens were subjected to periodic acid Schiff staining. Goblet cell density was quantified by J Image software. Quantitative real-time PCR for conjunctival muc 5AC messenger RNA expression was also performed. Results: Sod1-/- mice had significantly higher fluorescein staining scores compared to the WT mice before eye drop instillation. The mean tear film breakup time, Rose Bengal staining scores, and muc5 messenger RNA expression improved significantly with diquafosol treatment in both the WT and the knockout mice. The mean fluorescein staining score and aqueous tear quantity significantly improved in the Sod1-/- mice with treatment. A notable and consistent increase in goblet cells and decrease in inflammatory cell infiltrates could be confirmed in all specimens after 2 weeks of diquafosol eye drop application. Conclusions: Three percent diquafosol ophthalmic solution appears to be effective in the treatment of ocular surface disease in this age-related dry eye disease mouse model. © 2014 Molecular Vision.

Background: Retinitis pigmentosa (RP) is an inherited human retinal disorder that causes progressive photoreceptor cell loss, leading to severe vision impairment or blindness. However, no effective therapy has been established to date. Although genetic mutations have been identified, the available clinical data are not always sufficient to elucidate the roles of these mutations in disease pathogenesis, a situation that is partially due to differences in genetic backgrounds. Results: We generated induced pluripotent stem cells (iPSCs) from an RP patient carrying a rhodopsin mutation (E181K). Using helper-dependent adenoviral vector (HDAdV) gene transfer, the mutation was corrected in the patient's iPSCs and also introduced into control iPSCs. The cells were then subjected to retinal differentiation; the resulting rod photoreceptor cells were labeled with an Nrl promoter-driven enhanced green fluorescent protein (EGFP)-carrying adenovirus and purified using flow cytometry after 5 weeks of culture. Using this approach, we found a reduced survival rate in the photoreceptor cells with the E181K mutation, which was correlated with the increased expression of endoplasmic reticulum (ER) stress and apoptotic markers. The screening of therapeutic reagents showed that rapamycin, PP242, AICAR, NQDI-1, and salubrinal promoted the survival of the patient's iPSC-derived photoreceptor cells, with a concomitant reduction in markers of ER stress and apoptosis. Additionally, autophagy markers were found to be correlated with ER stress, suggesting that autophagy was reduced by suppressing ER stress-induced apoptotic changes. Conclusion: The use of RP patient-derived iPSCs combined with genome editing provided a versatile cellular system with which to define the roles of genetic mutations in isogenic iPSCs with or without mutation and also provided a system that can be used to explore candidate therapeutic approaches. © 2014 Yoshida et al.; licensee BioMed Central Ltd.