All

Li D, Li T, Paschalis EI, Wang H, Taniguchi EV, Choo Z-N, Shoji MK, Greenstein SH, Brauner SC, Turalba AV, Pasquale LR, Shen LQ. Optic Nerve Head Characteristics in Chronic Angle Closure Glaucoma Detected by Swept-Source OCT. Curr Eye Res 2017;42(11):1450-1457.Abstract
PURPOSE: To compare structural features in prelaminar and laminar tissues of the optic nerve head (ONH) in chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG), and control subjects. MATERIALS AND METHODS: ONH imaging was performed using swept-source optical coherence tomography (SS-OCT) for measurements of minimum rim width at Bruch's membrane opening (BMO-MRW), horizontal, and vertical lamina cribrosa depth (LCD). Prelaminar defects, categorized as hole and wedge, and lamina cribrosa (LC) defects were identified. Enhanced depth imaging spectral domain OCT (EDI-OCT) customized to perform high-resolution volume scans was used in conjunction to further characterize prelaminar holes. One eye per subject was analyzed. RESULTS: Eighty subjects (20 CACG, 40 POAG, and 20 controls) were included in the study. CACG and POAG groups had similar mean deviation on Humphrey visual field testing (-6.9 ± 5.1 vs. -6.3 ± 6.0 dB, p > 0.05) and IOP on the day of imaging (14.0 ± 3.1 vs. 13.8 ± 2.7 mmHg, p > 0.05). Thinnest and global BMO-MRW in CACG (120.3 ± 44.8, 225.5 ± 53.9 μm) and POAG (109.7 ± 56.3, 213.8 ± 59.7 μm) groups were lower than controls (200.1 ± 40.8, 308.3 ± 70.8 μm; p < 0.001 for both). Prelaminar holes were most frequent in CACG (65.0%) than POAG (25.0%, p=0.008) or control groups (20.0%, p=0.01). After adjusting for demographic and ophthalmic covariates, CACG was associated with increased odds of having prelaminar holes compared to POAG (odds ratio, 9.79; 95% CI, 2.12-45.19; p=0.003). Hole volume was similar between CACG and POAG (p > 0.05), but the CACG group had more holes per scan than POAG (maximum 2.5 ± 1.9 vs. 1.2 ± 0.4, p=0.02). Prelaminar wedge defects were less common in the CACG than the POAG group (5.0% vs. 37.5%, p=0.02). The CACG group did not differ from controls in laminar characteristics, such as LCD and LC defects. CONCLUSIONS: SS-OCT evaluation of the ONH revealed more frequent prelaminar holes in CACG compared to POAG and control patients.
Davies EC, Pineda R. Complications of Scleral-Fixated Intraocular Lenses. Semin Ophthalmol 2017;:1-6.Abstract
INTRODUCTION: Understanding the evolution of complications after scleral-fixated lens placement demonstrates advantageous surgical techniques and suitable candidates. MATERIALS/METHODS: A literature search in PubMed for several terms, including "scleral intraocular lens complication," yielded 17 relevant articles. RESULTS: Reviewing complication trends over time, lens tilt and suture erosion have decreased, cystoid macular edema has increased, and retinal detachment has remained the same after scleral-fixated lens placement. The successful reduction in complications are attributed to several alterations in technique, including positioning sclerotomy sites 180 degrees apart and using scleral flaps or pockets to bury sutures. Possible reduction in retinal risks have been proposed by performing an anterior vitrectomy prior to lens placement in certain settings. DISCUSSION: Complications after scleral-fixated lens placement should assist patient selection. Elderly patients with a history of hypertension should be counseled regarding risk of suprachoroidal hemorrhage, while young patients and postocular trauma patients should be considered for concurrent anterior vitrectomy.
Chwalisz B, Gilbert AL, Gittinger JW. Perioperative Vision Loss after Non-Ocular Surgery. Semin Ophthalmol 2017;:1-6.Abstract
Perioperative vision loss (POVL) may cause devastating visual morbidity. A prompt anatomical and etiologic diagnosis is paramount to guide management and assess prognosis. Where possible, steps should be undertaken to minimize risk of POVL for vulnerable patients undergoing high-risk procedures. We review the specific risk factors, pathophysiology, and management and prevention strategies for various etiologies of POVL.
Evangelista CB, Hatch KM. Corneal Collagen Cross-Linking Complications. Semin Ophthalmol 2017;:1-7.Abstract
Corneal cross-linking was approved by United States Food and Drug Administration for the treatment of progressive keratoconus in April 2016. As this approach becomes more widely used for the treatment of keratoconus and post-laser in situ keratomileusis (LASIK) ectasia, the medical community is becoming more familiar with potential complications associated with this procedure. This article aims to review the reported complications of collagen cross-linking for the treatment of keratoconus and post-LASIK ectasia.
Lippestad M, Hodges RR, Utheim TP, Serhan CN, Dartt DA. Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways. Invest Ophthalmol Vis Sci 2017;58(11):4530-4544.Abstract
Purpose: Goblet cells in the conjunctiva secrete mucin into the tear film protecting the ocular surface. The proresolution mediator resolvin D1 (RvD1) regulates mucin secretion to maintain homeostasis during physiological conditions and in addition, actively terminates inflammation. We determined the signaling mechanisms used by RvD1 in cultured rat conjunctival goblet cells to increase intracellular [Ca2+] ([Ca2+]i) and induce glycoconjugate secretion. Methods: Increase in [Ca2+]i were measured using fura 2/AM and glycoconjugate secretion determined using an enzyme-linked lectin assay with the lectin Ulex Europaeus Agglutinin 1. Signaling pathways activated by RvD1 were studied after goblet cells were pretreated with signaling pathway inhibitors before stimulation with RvD1. The results were compared with results when goblet cells were stimulated with RvD1 alone and percent inhibition calculated. Results: The increase in [Ca2+]i stimulated by RvD1 was blocked by inhibitors to phospholipases (PL-) -D, -C, -A2, protein kinase C (PKC), extracellular signal-regulated kinases (ERK)1/2 and Ca2+/calmodulin-dependent kinase (Ca2+/CamK). Glycoconjugate secretion was significantly inhibited by PLD, -C, -A2, ERK1/2 and Ca2+/CamK, but not PKC. Conclusions: We conclude that RvD1 increases glycoconjugate secretion from goblet cells via multiple signaling pathways including PLC, PLD, and PLA2, as well as their signaling components ERK1/2 and Ca2+/CamK to preserve the mucous layer and maintain homeostasis by protecting the eye from desiccating stress, allergens, and pathogens.
Charles NC, Jakobiec FA, Zakka FR, Haberman ID, Katikireddy KR, Jurkunas UV. Limbal Cysts: A Subset Exhibiting Cornea-Specific Cytokeratins. Ophthal Plast Reconstr Surg 2017;Abstract
Two cases of limbal cysts lined by nonkeratinizing epithelium were studied with a panel of cytokeratins. One was a long-standing lesion in a 30-year-old man, whereas the other was excised from a 40-year-old man following pterygium surgery. Each cyst was immunostained with a panel of cytokeratins that were specific exclusively and separately for corneal and conjunctival epithelia. The epithelial lining of each cyst was CK12 positive for corneal epithelium and CK13 negative for conjunctival epithelium. It is hypothesized that a subset of corneoscleral cysts contain corneal epithelium, probably derived from a type of limbal stem cell differentiation.
Olivares AM, Althoff K, Chen GF, Wu S, Morrisson MA, Deangelis MM, Haider N. Animal Models of Diabetic Retinopathy. Curr Diab Rep 2017;17(10):93.Abstract
PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. RECENT FINDINGS: Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.
Gupta PR, Huckfeldt RM. Gene therapy for inherited retinal degenerations: initial successes and future challenges. J Neural Eng 2017;14(5):051002.Abstract
Inherited retinal degenerations are a clinically and genetically heterogeneous group of conditions that have historically shared an untreatable course. In recent years, however, a wide range of therapeutic strategies have demonstrated efficacy in preclinical studies and entered clinical trials with a common goal of improving visual function for patients affected with these conditions. Gene therapy offers a particularly elegant and precise opportunity to target the causative genetic mutations underlying these monogenic diseases. The present review will provide an overview of gene therapy with particular emphasis on key clinical results to date and challenges for the future.
Au ED, Fernandez-Godino R, Kaczynksi TJ, Sousa ME, Farkas MH. Characterization of lincRNA expression in the human retinal pigment epithelium and differentiated induced pluripotent stem cells. PLoS One 2017;12(8):e0183939.Abstract
Long intervening non-coding RNAs (lincRNAs) are increasingly being implicated as important factors in many aspects of cellular development, function, and disease, but remain poorly understood. In this study, we examine the human retinal pigment epithelium (RPE) lincRNA transcriptome using RNA-Seq data generated from human fetal RPE (fRPE), RPE derived from human induced pluripotent stem cells (iPS-RPE), and undifferentiated iPS (iPS). In addition, we determine the suitability of iPS-RPE, from a transcriptome standpoint, as a model for use in future studies of lincRNA structure and function. A comparison of gene and isoform expression across the whole transcriptome shows only minimal differences between all sample types, though fRPE and iPS-RPE show higher concordance than either shows with iPS. Notably, RPE signature genes show the highest degree of fRPE to iPS-RPE concordance, indicating that iPS-RPE cells provide a suitable model for use in future studies. An analysis of lincRNAs demonstrates high concordance between fRPE and iPS-RPE, but low concordance between either RPE and iPS. While most lincRNAs are expressed at low levels (RPKM < 10), there is a high degree of concordance among replicates within each sample type, suggesting the expression is consistent, even at levels subject to high variability. Finally, we identified and annotated 180 putative novel genes in the fRPE samples, a majority of which are also expressed in the iPS-RPE. Overall, this study represents the first characterization of lincRNA expression in the human RPE, and provides a model for studying the role lincRNAs play in RPE development, function, and disease.
Jeng-Miller KW, Cestari DM, Gaier ED. Congenital anomalies of the optic disc: insights from optical coherence tomography imaging. Curr Opin Ophthalmol 2017;28(6):579-586.Abstract
PURPOSE OF REVIEW: Congenital anomalies of the optic nerve are rare but significant causes of visual dysfunction in children and adults. Accurate diagnosis is dependent on a thorough funduscopic examination, but can be enhanced by imaging information garnered from optical coherence tomography (OCT). We review common congenital optic nerve anomalies, including optic disc pit, optic nerve coloboma, morning glory disc anomaly, and hypoplasia of the optic nerve, review their systemic associations, and discuss insights from OCT imaging. RECENT FINDINGS: Optic disc pits are a result of a defect in the lamina cribrosa and abnormal vitreomacular adhesions have been shown to cause maculopathy. In patients with optic nerve colobomas, OCT can be instrumental in diagnosing choroidal neovascularization, a rare but visually devastating complication. The pathogenesis of morning glory disc anomaly has been more clearly elucidated by OCT as occurring from a secondary postnatal mesenchymal abnormality rather than only the initial neuroectodermal dysgenesis of the terminal optic stalk in isolation. OCT studies of optic nerve hypoplasia have demonstrated significant thinning of the inner and outer retinal layers of the perifoveal region and thicker layers in the fovea itself, resulting in a foveal hypoplasia-like pathology, that is, significantly correlated to poorer visual outcomes. SUMMARY: OCT provides detailed in-vivo analysis of these anatomic anomalies and their resulting pathologies, shedding new insights on the pathogenesis, diagnosis, and potential visual outcomes of these conditions in children. Further study employing OCT to elucidate structure-function relationships of congenital optic nerve anomalies will help expand the role of OCT in clinical practice related to diagnosis, prognosis, and management of these entities.
Hasegawa E, Inafuku S, Mulki L, Okunuki Y, Yanai R, Smith KE, Kim CB, Klokman G, Bielenberg DR, Puli N, Falck JR, Husain D, Miller JW, Edin ML, Zeldin DC, Stephen Lee KS, Hammock BD, Schunck W-H, Connor KM. Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization. Proc Natl Acad Sci U S A 2017;114(36):E7545-E7553.Abstract
Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.
Jackson CJ, Reppe S, Eidet JR, Eide L, Tønseth KA, Bergersen LH, Dartt DA, Griffith M, Utheim TP. Optimization of Storage Temperature for Retention of Undifferentiated Cell Character of Cultured Human Epidermal Cell Sheets. Sci Rep 2017;7(1):8206.Abstract
Cultured epidermal cell sheets (CES) containing undifferentiated cells are useful for treating skin burns and have potential for regenerative treatment of other types of epithelial injuries. The undifferentiated phenotype is therefore important for success in both applications. This study aimed to optimize a method for one-week storage of CES for their widespread distribution and use in regenerative medicine. The effect of storage temperatures 4 °C, 8 °C, 12 °C, 16 °C, and 24 °C on CES was evaluated. Analyses included assessment of viability, mitochondrial reactive oxygen species (ROS), membrane damage, mitochondrial DNA (mtDNA) integrity, morphology, phenotype and cytokine secretion into storage buffer. Lowest cell viability was seen at 4 °C. Compared to non-stored cells, ABCG2 expression increased between temperatures 8-16 °C. At 24 °C, reduced ABCG2 expression coincided with increased mitochondrial ROS, as well as increased differentiation, cell death and mtDNA damage. P63, C/EBPδ, CK10 and involucrin fluorescence combined with morphology observations supported retention of undifferentiated cell phenotype at 12 °C, transition to differentiation at 16 °C, and increased differentiation at 24 °C. Several cytokines relevant to healing were upregulated during storage. Importantly, cells stored at 12 °C showed similar viability and undifferentiated phenotype as the non-stored control suggesting that this temperature may be ideal for storage of CES.
Norsworthy MW, Bei F, Kawaguchi R, Wang Q, Tran NM, Li Y, Brommer B, Zhang Y, Wang C, Sanes JR, Coppola G, He Z. Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others. Neuron 2017;94(6):1112-1120.e4.Abstract
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration. Transcriptome profiling indicated that Sox11 activates genes involved in cytoskeletal remodeling and axon growth. Remarkably, α-RGCs, which preferentially regenerate following treatments such as Pten deletion, were killed by Sox11 overexpression. Thus, Sox11 promotes regeneration of non-α-RGCs, which are refractory to Pten deletion-induced regeneration. We conclude that Sox11 can reprogram adult RGCs to a growth-competent state, suggesting that different growth-promoting interventions promote regeneration in distinct neuronal types.

Pages