Systemic approaches using single cell transcriptome reveal that C/EBPγ regulates autophagy under amino acid starved condition.

Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein γ (C/EBPγ) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBPγ for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBPγ as a previously unidentified key regulator under AAS-induced autophagy.

RORα is crucial for attenuated inflammatory response to maintain intestinal homeostasis.

Retinoic acid-related orphan receptor α (RORα) functions as a transcription factor for various biological processes, including circadian rhythm, cancer, and metabolism. Here, we generate intestinal epithelial cell (IEC)-specific RORα-deficient (RORαΔIEC) mice and find that RORα is crucial for maintaining intestinal homeostasis by attenuating nuclear factor κB (NF-κB) transcriptional activity. RORαΔIEC mice exhibit excessive intestinal inflammation and highly activated inflammatory responses in the dextran sulfate sodium (DSS) mouse colitis model. Transcriptome analysis reveals that deletion of RORα leads to up-regulation of NF-κB target genes in IECs. Chromatin immunoprecipitation analysis reveals corecruitment of RORα and histone deacetylase 3 (HDAC3) on NF-κB target promoters and subsequent dismissal of CREB binding protein (CBP) and bromodomain-containing protein 4 (BRD4) for transcriptional repression. Together, we demonstrate that RORα/HDAC3-mediated attenuation of NF-κB signaling controls the balance of inflammatory responses, and therapeutic strategies targeting this epigenetic regulation could be beneficial to the treatment of chronic inflammatory diseases, including inflammatory bowel disease (IBD).

Spontaneous regression of congenital corneal opacity.

PURPOSE: To determine the incidence of spontaneous regression of congenital corneal opacity (CCO) and identify clinical factors associated with the regression. METHODS: Medical records and anterior segment photographs were reviewed of 57 eyes in 35 patients with CCO that were not related to congenital glaucoma, tumors, infection, trauma, or metabolic disorders and were followed up without corneal transplantation for longer than one year at Seoul National University Hospital. Spontaneous regression of corneal opacity was defined as a decrease in corneal opacity significant enough for visual axis clearance. Data on demographics, systemic, and ocular characteristics were collected and compared between patients who had spontaneous regression of CCO and those who did not. RESULTS: Spontaneous regression of corneal opacity developed in 32 eyes (22 patients, 56.1%) out of 57 CCO eyes (35 patients) at the mean 8.2 ± 5.4 months of age (the median 6.7 months). Absence of combined ocular anomalies such as iris anomaly, lens opacity, and peripheral corneal vascularization was significantly associated with the regression of opacity. CONCLUSIONS: Corneal opacity can spontaneously regress in 56.1% of eyes with CCO during the first year of life. Careful follow-up with amblyopia management can be one of treatment options for CCO.

Long-term surgical outcomes of patients with consecutive exotropia.

PURPOSE: To evaluate the long-term surgical outcome of patients with consecutive exotropia. METHODS: Patients who underwent surgery for the treatment of consecutive exotropia between January 2008 and July 2016 with a minimum follow-up period of 2 years were retrospectively reviewed. Surgical outcomes were classified based on postoperative angle of deviation at 2 years as follows: success (esodeviation ≤ 5 prism diopters [PD] to exodeviation ≤ 10 PD), and recurrence [exodeviation > 10 PD]). Postoperative angles of deviation at 1 week, 1 month, 6 months, 1 year, and 2 years and at the final follow-up were investigated. RESULTS: A total of 37 patients (28 in the success group and 9 in the recurrence group) were included. Surgical success rate at 2 years was 75.7%, and reoperation rate was 10.8% during a mean follow-up period of 42.4 ± 18.3 months after consecutive exotropia surgery. After surgery, exodrift occurred mostly during 1-month follow-up in both groups, and those with no exodrift within 1 month presented a higher surgical success. Thereafter, patients in the success group showed a more stable course during follow-up than those in the recurrence group. Stereopsis was an important factor associated with surgical outcome. CONCLUSIONS: Exodrift occurs mostly within 1 month after surgery for consecutive exotropia. Targeting initial overcorrection and establishing esodeviation at postoperative month 1 is important to achieve successful results.

Factors Associated with the Prognosis after Operation in Children with Recurrent Intermittent Exotropia.

BACKGROUND: To describe factors affecting the prognosis after operation for recurrent intermittent exotropia (X[T]) in children. METHODS: Clinical records of 50 patients who underwent operation for recurrent X(T) by a single surgeon were reviewed. The age at diagnosis of X(T), and first and second operations, deviation angle at distance and near, surgical method, concurrent vertical strabismus, stereoacuity, and Worth's Four Dot (W4D) examination before reoperation were analyzed, along with the postoperative deviation angle. A successful surgical outcome was defined as orthophoria, esodeviation ≤ 5 prism diopters, or exodeviation ≤ 10 prism diopters at distance. RESULTS: Among the 50 recurrent exotropes who underwent surgery and were followed up for more than 1 year postoperatively, 13 showed recurrent exotropia and 1 showed consecutive esotropia. The mean age at reoperation was 8.49 ± 2.19 years, and the mean duration of postoperative follow-up was 27.78 ± 12.02 months. Good near fusion before reoperation was a significant factor in the success of surgery (P = 0.006). Smaller postoperative deviation angle measured immediately and 2 months after surgery were related to smaller final deviation angle (P = 0.027 and P = 0.022, respectively). CONCLUSION: Peripheral suppression lowers the success rate of operation for recurrent X(T) in children. Overcorrection rather than orthotropia should be the target of immediate postoperative deviation angle. Peripheral suppression status and immediate and 2-month postoperative deviation angle may be important clues for predicting the final result of operation for recurrent X(T).

Outcomes of Proton Beam Radiation Therapy for Retinoblastoma With Vitreous Seeds.

Vitreous seeds are the most challenging aspect in the management of retinoblastoma. We report the outcomes of treatment with proton beam radiation therapy (PBRT) for retinoblastoma with vitreous seeds in naive or previously treated eyes. In this retrospective case series, we analyzed data of 4 retinoblastoma patients with vitreous seeds who received PBRT at the Proton Therapy Center, National Cancer Center in Korea between June 2007 and August 2017. All 4 eyes treated by PBRT were classified as group D according to the International Classification of Retinoblastoma (ICRB) criteria, and the vitreous seeds, as class 3 (clouds). The tumor and vitreous seeds regressed in 2 eyes, and globe salvage was achieved in these 2 eyes (50%). The post-PBRT ophthalmologic follow-up time of these 2 preserved eyes was 12 and 50 months, respectively. Visual acuity measurements of the successfully treated patients were 20/40 and 20/600. No radiation-associated malignancies were noted. In conclusion, PBRT successfully treated vitreous seeds classified as clouds in half of the cases, and successfully treated patients who retained useful vision. Therefore, PBRT might be a viable treatment option for vitreous seeds in patients with retinoblastoma.

Clinical features and outcome of corneal opacity associated with congenital glaucoma.

BACKGROUND: To investigate the clinical features of corneal opacity and the surgical outcome of penetrating keratoplasty (PK) in eyes with congenital glaucoma. METHODS: A retrospective review was made of the records from 320 eyes of 193 patients who were diagnosed with congenital glaucoma between January 1981 and January 2016. Anterior segment photographs at disease presentation were examined for the presence and severity of corneal opacity. Data on patient demographics, intraocular pressure (IOP), ocular and systemic comorbidities, ocular surgery and its outcome were collected. RESULTS: Overall, corneal opacification was observed in 248 of 320 eyes (77.5%). Out of 248 eyes with corneal opacification, 53 eyes had Haab striae alone, and 195 eyes presented with either nebulomacular corneal opacity (128 eyes, iris details visible through opacity) or leukomatous corneal opacity (67 eyes, iris details invisible through opacity). In 12 eyes with severe leukomatous corneal opacity, PK was performed at the mean age of 18.6 months (range 4-57 months). The grafts failed in 6 eyes (50%) due to endothelial rejection (4 eyes) or graft infection (2 eyes) during the mean 80.6 months of follow-up (range 15-228 months). The median survival time was 36 months. The graft failure was significantly associated with smaller corneal diameter at the time of surgery, but not with the age, IOP, combined aniridia, simultaneous glaucoma or lens surgery. CONCLUSION: Congenital glaucoma was combined with corneal opacity in 77.5%. The corneal transplant survival was 50% in eyes with congenital glaucoma and total corneal opacity.

Effects on Periocular Tissues after Proton Beam Radiation Therapy for Intraocular Tumors.

BACKGROUND: To present our experience on orbital and periorbital tissue changes after proton beam radiation therapy (PBRT) in patients with intraocular tumors, apart from treatment outcomes and disease control. METHODS: Medical records of 6 patients with intraocular tumors who had been treated with PBRT and referred to oculoplasty clinics of two medical centers (Seoul National University Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center) from October 2007 to September 2014 were retrospectively reviewed. The types of adverse effects associated with PBRT, their management, and progression were analyzed. In anophthalmic patients who eventually underwent enucleation after PBRT due to disease progression, orbital volume (OV) was assessed from magnetic resonance (MR) images using the Pinnacle3 program. RESULTS: Among the six patients with PBRT history, three had uveal melanoma, and three children had retinoblastoma. Two eyes were treated with PBRT only, while the other four eyes ultimately underwent enucleation. Two eyes with PBRT only suffered from radiation dermatitis and intractable epiphora due to canaliculitis or punctal obstruction. All four anophthalmic patients showed severe enophthalmic features with periorbital hollowness. OV analysis showed that the difference between both orbits was less than 0.1 cm before enucleation, but increased to more than 2 cm³ after enucleation. CONCLUSION: PBRT for intraocular tumors can induce various orbital and periorbital tissue changes. More specifically, when enucleation is performed after PBRT due to disease progression, significant enophthalmos and OV decrease can develop and can cause poor facial cosmesis as treatment sequelae.

Very late relapse of bilateral retinoblastoma.

Retinoblastoma usually recurs within the first few years after treatment completion. We report a rare case of very late relapse in a 6-month-old girl who was diagnosed with bilateral retinoblastoma. The patient achieved first remission after treatment with neoadjuvant chemotherapy, enucleation of the right eye, local laser therapy of the left eye, and adjuvant chemotherapy. Extraocular relapse with multiple metastases occurred 13 years and 8 months after treatment. The patient is currently in second complete remission after receiving high-dose chemotherapy and autologous stem cell transplantation. In conclusion, long-term follow-up is needed for early detection of recurrent retinoblastoma.

Atypical retinopathy in patients with nephronophthisis type 1: an uncommon ophthalmological finding.

BACKGROUND: Progressive retinal degeneration without retinal pigmentation has been repeatedly observed in Korean nephronophthisis (NPHP) type 1 patients with a total homozygous deletion of NPHP1. DESIGN: Retrospective case series. PARTICIPANTS: Patients with clinical diagnosis of NPHP and genetic diagnosis of total deletion of NPHP1 (n = 5) were included in this study. METHODS: Patients with clinical diagnosis of NPHP (n = 57) were screened for total deletion of NPHP1 by polymerase chain reaction (PCR) for the 20 exons of NPHP1. The clinical and ophthalmological findings of NPHP type 1 patients were reviewed. Additionally, four exons of MALL, a gene adjacent to NPHP1, were amplified using PCR, and amplification failure was considered a homozygous deletion encompassing the corresponding exons. MAIN OUTCOME MEASURE: Ophthalmological findings in NPHP type 1 patients. RESULTS: Five of 57 patients with clinical diagnosis of NPHP were diagnosed as having NPHP type 1 by genetic analysis. Chronic renal failure was diagnosed in these five patients at 7.9-15.4 years of age. All the patients with NPHP type 1 had progressive decline in visual acuity with various ages of onset (2-17 years). Ophthalmological examinations revealed unexpected findings of retinopathy with large or small flecks, which was compatible with Stargardt-like retinopathy or albipunctatus retinopathy in majority of them (four of five). The genetic study revealed an additional deletion of exon 1 of the adjacent gene MALL. CONCLUSIONS: We report the unexpectedly common retinal involvement of NPHP type 1 with an additional MALL deletion in a Korean cohort.

Suppression of protein kinase C-ζ attenuates vascular leakage via prevention of tight junction protein decrease in diabetic retinopathy.

To investigate the effect of protein kinase C (PKC)-ζ inhibition on vascular leakage in diabetic retinopathy, streptozotocin-induced diabetic mice were intravitreously injected with siPKC-ζ. According to the fluorescein angiography of the retinal vessels, suppression of PKC-ζ effectively attenuated vascular leakage in diabetic retina. Further evaluation on the retina with western blot analysis and immunohistochemistry revealed accompanying restoration of tight junction proteins on retinal vessels. As two major contributors to vascular leakage in diabetic retinopathy, vascular endothelial growth factor (VEGF) and advanced glycation end products (AGEs) were investigated on the tight junction protein expression in endothelial cells. Inhibition of PKC-ζ attenuated VEGF-induced decrease of tight junction proteins and accompanying hyperpermeability in human retinal microvascular endothelial cells (HRMECs). PKC-ζ inhibition also attenuated AGE-induced decrease of tight junction proteins in HRMECs. Our findings suggest that inhibition of PKC-ζ could be an alternative treatment option for compromised blood-retinal barrier in diabetic retinopathy.

Anti-angiogenic effect of bare titanium dioxide nanoparticles on pathologic neovascularization without unbearable toxicity.

Local application requires fewer nanoparticles than systemic delivery to achieve effective concentration. In this study, we investigated the potential toxicity and efficacy of bare titanium dioxide (TiO2) nanoparticles by local administration into the eye. Mono-disperse, 20nm-size TiO2 nanoparticles did not affect the viability of retinal constituent cells within certain range of concentrations (~1.30µg/mL). Furthermore, local delivery of TiO2 nanoparticles did not induce any significant toxicity at the level of gene expression and histologic integrity in the retina of C57BL/6 mice. Interestingly, at the low concentration (130ng/mL) without definite toxicity, these nanoparticles suppressed in vitro angiogenesis processes and in vivo retinal neovascularization in oxygen-induced retinopathy mice when they are administered intravitreally. Taken together, our results demonstrate that even TiO2 nanoparticles can be safely utilized for the treatment of retinal diseases at the adequate concentration levels, especially through local administration. FROM THE CLINICAL EDITOR: In this paper the local application of titanium dioxide is described as a local treatment for retinal diseases associated with neovascularization. While these nanoparticles have known systemic toxicity, this work demonstrates that when applied locally in a mouse model, they can be used without observable toxicity even in their native forms.

Changes in Visual Function over Time in Koreans with Non-arteritic Anterior Ischaemic Optic Neuropathy.

Non-arteritic anterior ischaemic optic neuropathy (NAION) causes severe visual loss in elderly patients. However, there are not much data of clinical course of NAION in Asian patients. To evaluate changes in visual acuity and visual field defects associated with non-arteritic anterior ischaemic optic neuropathy (NAION) among Korean patients, the medical records of 50 eyes from 43 patients with NAION patients seen from 1989 to 2011 were reviewed. A significant change in visual acuity was defined as a three-line change in Snellen acuity. Visual field defects were evaluated with Goldmann perimetry. Changes in the visual field were evaluated using the grid method. Thirty-eight percent of eyes showed improvement, 54% showed no change, and 8% showed deterioration of visual acuity at the last follow-up. Thirty-four percent of eyes showed improvement, 54% showed no change, and 12% showed deterioration of the visual field at the last follow-up. Most improvement in visual acuity occurred during the first month after the initial visit and in visual field between the first and third months of follow-up. The prognosis of visual acuity in association with NAION was worse in Korean patients as compared with Western studies. However, improved prognosis of visual field defects might come from the use of different methods for evaluation of the visual field.

Orthotopic transplantation of retinoblastoma cells into vitreous cavity of zebrafish for screening of anticancer drugs.

BACKGROUND: With high throughput screening, novel therapeutic agents can be efficiently identified. Unfortunately, researchers only resort to in vitro cell viability assays for screening of anticancer drugs for retinoblastoma, the most common intraocular cancer in the childhood. Current available animal models of retinoblastoma require more than 2 weeks for tumour formation and the investigation of the efficacy of therapeutic agents. In this study, we established a novel orthotopic transplantation model of retinoblastoma in zebrafish as an in vivo animal model for screening of anticancer drugs. METHODS: We injected retinoblastoma cells into the vitreous cavity of zebrafish at 48 hours after fertilization. Eyeballs of zebrafish were scanned daily under the confocal laser microscope, and the tumor population was quantitatively analyzed by measuring the mean intensity of green fluorescent protein (GFP). Transplanted retinoblastoma cells were isolated to perform further analyses including Western blotting and reverse transcriptase-polymerase chain reaction to confirm that retinoblastoma cells maintained their characteristics as tumor cells even after transplantation and further isolation. To figure out the potential of this model for screening of anticancer drugs, zebrafish were cultured in Ringer's solution containing carboplatin and melphalan after the injection of retinoblastoma cells. RESULTS: The degree of the tumor population was dependent on the number of retinoblastoma cells injected and maintained stably for at least 4 days. Transplanted retinoblastoma cells maintain their proliferative potential and characteristics as retinoblastoma cells after isolation. Interestingly, systemic application of carboplatin and melphalan demonstrated significant reduction in the tumor population, which could be quantitatively analyzed by the estimation of the mean intensity of GFP. CONCLUSIONS: This orthotopic retinoblastoma model in zebrafish is expected to be utilized for the screening of anticancer drugs for the treatment of retinoblastoma.

Pathogenic mutations in two families with congenital cataract identified with whole-exome sequencing.

PURPOSE: Congenital cataract is one of the most frequent causes of visual impairment and childhood blindness. Approximately one quarter to one third of congenital cataract cases may have a genetic cause. However, phenotypic variability and genetic heterogeneity hamper correct genetic diagnosis. In this study, we used whole-exome sequencing (WES) to identify pathogenic mutations in two Korean families with congenital cataract. METHODS: Two affected members from each family were pooled and processed for WES. The detected variants were confirmed with direct sequencing. RESULTS: WES readily identified a CRYAA mutation in family A and a CRYGC mutation in family B. The c.61C>T (p.R21W) mutation in CRYAA has been previously reported in a family with congenital cataract and microcornea. The novel mutation, c.124delT, in CRYGC may lead to a premature stop codon (p.C42Afs*60). CONCLUSIONS: This study clearly shows the efficacy of WES for rapid genetic diagnosis of congenital cataract with an unknown cause. WES will be the first choice for clinical services in the near future, providing useful information for genetic counseling and family planning.

NK cell-associated antigen expression in retinoblastoma animal model.

Natural killer (NK) cells are critical components of our immune system. Herein, we for the first time analyzed the expression and localization of the activating receptor NK cell lectin-like receptor gene 2D (NKG2D) ligands, HLA-G, MICA, MICA/B, and ULBP-2 in orthotopic transplantation models of retinoblastoma. Interestingly, HLA-G and MICA/B were expressed in retinoblastoma cell, whereas MICA and ULBP-2 were not detected. Moreover, HLA-G and MICA/B were primarily detected in proliferative area of the tumor periphery with high Ki-67 immunostaining. Our results suggest that NKG2D ligands are differentially expressed in retinoblastoma, which would play a crucial role in immunomodulation in retinoblastoma.

Spectral-domain optical coherence tomography analysis in deprivational amblyopia: a pilot study with unilateral pediatric cataract patients.

BACKGROUND: To investigate whether macular and peripapillary retinal nerve fiber layer (RNFL) structure differs among deprivational amblyopic eyes, fellow non-amblyopic eyes, and age-matched normal eyes, using spectral-domain optical coherence tomography (SD-OCT). METHODS: Macula and optic disc of 14 unilateral pseudophakic children with deprivational amblyopia, and 14 age-matched normal children (mean age, 7.45 ± 2.57 years) were scanned with Cirrus(TM) HD-OCT. Macular, RNFL, and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured, and compared between the eyes after correction for axial length-related magnification errors. RESULTS: The average RNFL thickness tended to be greater in amblyopic eyes (99.64 ± 10.11 µm) than in fellow non-amblyopic eyes (97.28 ± 12.34 µm) and normal eyes (95.38 ± 9.74 µm), but did not show statistical significance (p = 0.429, p = 0.286 respectively). The nasal RNFL thickness was significantly greater in amblyopic eyes (75.84 ± 19.22 µm) than in fellow non-amblyopic eyes (63.42 ± 14.05 µm, p = 0.037) and normal eyes (62.38 ± 9.65 µm, p = 0.043). The central macular thickness in amblyopic eyes (237.05 ± 37.74 µm) showed no significant differences compared to those of fellow non-amblyopic eyes (226.67 ± 34.71 µm) and normal eyes (233.74 ± 27.11 µm) (p = 0.137, p = 0.792 respectively). The macular GCIPL thickness showed no significant difference among the amblyopic, fellow non-amblyopic, and normal eyes (average; 78.94 ± 6.35 µm vs 78.77 ± 6.43 µm vs 82.22 ± 5.00 µm respectively, p > 0.05). CONCLUSIONS: SD-OCT analysis of deprivational amblyopic eyes with unilateral pediatric cataract demonstrated significant increase in nasal RNFL thickness compared to fellow non-amblyopic eyes and age-matched normal eyes. The macular and macular GCIPL thickness did not show any significant difference. Taken together, monocular pattern deprivation in early childhood may have changed the nasal peripapillary RNFL structure.

Long-term visual outcomes of penetrating keratoplasty for Peters anomaly.

BACKGROUND: To investigate the long-term results and visual outcomes of penetrating keratoplasty (PKP) in Peters anomaly. METHODS: Twenty-three eyes from 22 patients with Peters anomaly who underwent PKP from 1998 to 2008 were reviewed retrospectively. Patients who were followed for more than 3 years after the first PKP were included in this study. The systemic and ophthalmic features of the recipients were assessed, and the various prognostic factors for graft survival were evaluated. Disease severity was determined according to other accompanying eye anomalies in mild or severe form. The final visual outcomes were presented with respect to graft clarity. RESULTS: Among the 22 patients, 14 patients had unilateral disease, and eight patients had bilateral disease. Associated systemic anomalies were observed in six patients. The mean age at the first PKP was 42.4 months. Nineteen eyes (83 %) underwent PKP after 12 months of age. The graft failure rates at 1 year, 3 years, 5 years, and 10 years after PKP were 30 %, 39 %, 70 %, and 77 % respectively. Graft rejection within 1 month after PKP and severe disease were significant risk factors for graft failure. The mean final VAs in the clear-graft group and the failed-graft group were 1.883 logMAR and 2.767 logMAR (P < 0.001). CONCLUSION: The results of delayed PKP in Peters anomaly were not inferior compared to the results of PKP performed at an earlier period in previous studies. If other congenital ophthalmic anomalies were present or graft rejection occurred within 1 month after PKP, the chance of graft failure was significantly increased.

Prognostic factors for visual recovery after transsphenoidal pituitary adenectomy.

OBJECTIVES: Pituitary adenomas often cause deficits in visual acuity (VA) and visual field (VF) due to compression of the optic chiasm. This study is to identify factors most likely to predict the prognosis of VA and VF after transsphenoidal pituitary adenectomy. MATERIALS AND METHODS: Clinical records of patients who underwent transsphenoidal pituitary adenectomy were retrospectively reviewed. Data analysed included systemic and visual symptom duration, tumour size, presence of suprasellar tumour extension, histological classification of tumour, VA, and VF. VFs were determined using the Goldmann VF test and quantified according to methods outlined by the American Medical Association. RESULTS: One-hundred and seventy eyes from 85 patients were included. Systemic and visual symptom duration, pre- and postoperative tumour size, and age did not correlate with postoperative VA or VF score. Patients with normal preoperative VA had a better postoperative VA than that of patients with preoperative VA of 20/30 or worse. Patients with normal preoperative VA had better postoperative VF score than that of patients with preoperative VA of 20/70 or worse. Postoperative VF score was lower in the preoperative ≥ 2 quadrant field loss group than in the ≤ 1 quadrant field loss group. Postoperative VA was worse in the ≥ 2 quadrant loss group than in the normal field group. Preoperative VA correlated with postoperative VA and VF score, and preoperative VF score correlated with postoperative VF score but not with VA. CONCLUSIONS: Preoperative VA is a prognostic factor for postoperative VA and VF. Preoperative VF is predictive of postoperative VF and postoperative VA in cases with severe VF loss.

Epigenetic regulation of autophagy by histone-modifying enzymes under nutrient stress.

Autophagy is an evolutionarily conserved catabolic process that is induced in response to various stress factors in order to protect cells and maintain cellular homeostasis by degrading redundant components and dysfunctional organelles. Dysregulation of autophagy has been implicated in several conditions such as cancer, neurodegenerative diseases, and metabolic disorders. Although autophagy has been commonly considered as a cytoplasmic process, accumulating evidence has revealed that epigenetic regulation within the nucleus is also important for regulation of autophagy. In particular, when energy homeostasis is disrupted, for instance due to nutrient deprivation, cells increase autophagic activity at the transcriptional level, thereby also increasing the extent of overall autophagic flux. The transcription of genes associated with autophagy is strictly regulated by epigenetic factors through a network of histone-modifying enzymes along with histone modifications. A better understanding of the complex regulatory mechanisms of autophagy could reveal potential new therapeutic targets for autophagy-related diseases. In this review, we discuss the epigenetic regulation of autophagy in response to nutrient stress, focusing on histone-modifying enzymes and histone modifications.