Regulation of Reentrainment Function Is Dependent on a Certain Minimal Number of Intact Functional ipRGCs in rd Mice

Purpose. To investigate the effect of partial ablation of melanopsin-containing retinal ganglion cells (mcRGCs) on nonimage-forming (NIF) visual functions in rd mice lacking rods. Methods. The rd mice were intravitreally injected with different doses (100 ng/μl, 200 ng/μl, and 400 ng/μl) of immunotoxin melanopsin-SAP. And then, the density of ipRGCs was examined. After establishing the animal models with different degrees of ipRGC damage, a wheel-running system was used to evaluate their reentrainment response. Results. Intravitreal injection of melanopsin-SAP led to partial ablation of ipRGCs in a dose-dependent manner. The survival rates of ipRGCs in the 100 ng/μl, 200 ng/μl, and 400 ng/μl groups were 74.14% ± 4.15%, 39.25% ± 2.29%, and 38.38% ± 3.74%, respectively. The wheel-running experiments showed that more severe ipRGC loss was associated with a longer time needed for reentrainment. When the light/dark cycle was delayed by 8 h, the rd mice in the PBS control group took 4.67 ± 0.79 days to complete the synchronization with the shifted cycle, while those in the 100 ng/μl and 200 ng/μl groups required 7.90 ± 0.55 days and 11.00 ± 0.79 days to complete the synchronization with the new light/dark cycle, respectively. Conclusion. Our study indicates that the regulation of some NIF visual functions is dependent on a certain minimal number of intact functional ipRGCs

Dry Eye Syndrome in Patients with Diabetes Mellitus: Prevalence, Etiology, and Clinical Characteristics

There has been substantial progress in our understanding of the ocular surface system/lacrimal function unit in the past 15 years. Keratoconjunctivitis sicca, more commonly referred to as dry eye syndrome (DES), is the most frequently encountered condition and diabetes mellitus (DM) has been identified as one of the leading causes of DES. Poor glycemic control affects both the anterior and the posterior segments of the eye and increasing prevalence of diabetes-associated DES (DMDES) has been reported in recent years. The pathogenesis and specific features of DMDES remain uncertain and interventions are limited to those used in DES. This review outlines the pathogenesis, clinical manifestations, and the current preventive and treatment strategies for diabetes-related DES

Bulk Molybdenum Spindt Field Emission Arrays

This is the final version of the article. It first appeared from One Central Press via http://www.onecentralpress.com/bulk-molybdenum-spindt-field-emission-arrays/.This paper reports on a simple approach for fabricating modest aspect ratio field emission arrays (FEAs) directly from bulk molybdenum substrates via the use of fluorine inductive-coupled-plasma (ICP) etching. Compared to traditional Spindt array fabrication, through our outlined fabrication process all thin film interfaces have been eliminated reducing tip delamination during operation. The as-fabricated devices exhibited low turn-on electric fields (I = 100nA) of 1.21 V/μm. Arrays of more than 10$^6$ tips, with controlled inter-tip-pitches of 10 μm, have produced maximum currents of up to 140 μA (5.48 V/μm). Spatially uniform emission, that can be white light optically modulated, has been observed making our Mo-FEAs promising for use in long-term, high beam current continuous emission applications.Oppenheimer Trus

Retinotopic changes in the gray matter volume and cerebral blood flow in the primary visual cortex of patients with primary open-angle glaucoma

PURPOSE. To assess the cortical structure and cerebral blood flow changes in the brain of patients with primary open-angle glaucoma (POAG). METHODS. High-resolution anatomical magnetic resonance imaging (MRI) and arterial spin labeling (ASL)-MRI were performed in 23 POAG patients and 29 controls. Patients were further divided into early-moderate and advanced groups based on mean deviation (MD) cutoff of 12 dB. A baseline scan was obtained and repeated during visual stimulation to the central preserved visual field in the more affected eye of POAG patients and a randomly selected eye of controls. Gray matter volume (GMV) and cerebral blood flow (CBF) throughout the whole brain were compared between patients and controls. RESULTS. Compared to controls, a region with significant reduction of GMV was detected in the anterior calcarine fissure of advanced POAG patients (P < 0.001, voxels = 503, 1698 mm). Patients with early-moderate POAG had resting CBF similar to that of controls. However, a region with marked CBF decrease was detected in the anterior calcarine fissure of advanced POAG patients (P < 0.001, voxels = 1687, 13,496 mm). The region with CBF reduction in advanced POAG showed good colocalization with the region with GMV decrease in this group. Following visual stimulation, patients with advanced POAG showed significantly lower increase in CBF in the occipital lobes (P < 0.001, voxels = 112, 896 mm) as compared to controls (P < 0.001, voxels = 1880, 15,040 mm) and early-moderate POAG (P < 0.001, voxels = 2233, 17,864 mm). CONCLUSIONS. Primary open-angle glaucoma patients demonstrate a disease severity–dependent retinotopic pattern of cortical atrophy and CBF abnormalities in the visual cortex. Cerebral blood flow may be a potential biomarker for the brain involvement in glaucoma

Evaluation of LOXL1 polymorphisms in exfoliation syndrome in a Chinese population

Purpose: To evaluate the association profiles of the lysyl oxidase-like 1 (LOXL1) gene polymorphisms with exfoliation syndrome in a Chinese population. Methods: Fifty unrelated patients with exfoliation syndrome and 125 control subjects were included. Genotypes of the three single nucleotide polymorphisms (SNPs) of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed by direct sequencing, and a case-control association study was performed. Results: The three SNPs were significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) individually. After controlling for rs3825942 and rs2165241, the association between rs1048661 and XFS/XFG remained significant (p=3.6x10(-7)). At this SNP, the T allele and TT genotype conferred a 7.59-(95% confidence interval [CI]: 3.87-14.89, p=6.95x10(-11)) and 8.69-(95% CI: 4.15-18.20, p&lt;1.00x10(-7)) fold increased risk to the disease. The alleles of T at rs1048661 and C at rs2165241 were found to be risk alleles in Chinese subjects, which were opposite to Caucasian individuals. The haplotypes T-G, defined by SNPs rs1048661 and rs3825942, and T-C by SNPs rs1048661 and rs2165241, were also significantly associated with the disorder. However when the genotypic or allelic frequencies of the three SNPs were compared between XFS and XFG, no significant difference was detected. Conclusions: LOXL1 is a susceptibility gene of XFS/XFG in the Chinese population, and the association is mainly attributed to SNP rs1048661. The risk alleles of rs1048661 and rs2165241 in Chinese subjects were found to be opposite to that of Caucasians. The genotypic and allelic distributions of these SNPs are similar between XFS and XFG.Biochemistry &amp; Molecular BiologyOphthalmologySCI(E)30ARTICLE250-522349-23571

Using the Utah Population Database to assess familial risk of primary open angle glaucoma

AbstractPurposePrimary open angle glaucoma (POAG) is a leading cause of irreversible blindness in the elderly. Previous epidemiological studies have identified family history, ethnic origin, age, high intraocular pressure and diabetes mellitus as risk factors. However, it is difficult to assess the extent family history plays in this disease process. The Utah Population Database (UPDB), created by the University of Utah, has recently become a resource for which greater than 9 million records are available for use. The UPDB is divided into two major data sets from which family members can be identified, namely 1.6 million genealogy records and 2 million Utah birth certificates. This study utilizes these resources to assess the familial risk of POAG within the Utah Population.MethodsThe University of Utah’s hospital and clinic records were searched for patients with primary and chronic open angle glaucoma (ICD9 codes 365.04 and 365.11) between the years 1995 and 2005. A case-control analysis was then performed with specialized UPDB software that was modified to constrain the control and pedigree populations to over 1 million University of Utah-UPDB linked records. Controls were matched to cases by gender and birth year (±2.5years) with only one control being used per case. Population-attributable risk (PAR) to familial factors and relative risk (RR) were computed using conditional logistic regression (CLR).ResultsFrom the original 1.5 million medical records, 6198 patients with glaucoma were identified. Of these, 3391 met the inclusion criteria, which required patients to have at least one parent or one child in the UPDB. The PAR in this population was found to be 0.20, indicating 20% of the risk for glaucoma is attributable to genetic factors. CLR computations also showed a significantly increased relative risk (p<0.05) in first cousins (RR=1.45 (95% confidence interval (CI) 1.16–1.8)), second cousins (RR=1.19 (95% CI 1.08–1.32)), siblings (RR=3.76 (95% CI 2.66–5.31)), parents (RR=6.25 (95% CI 3.94–9.9)) and children (RR=6.77 (95% CI 3.39–13.5)).ConclusionsBased on these familial data, there is a significantly higher prevalence of glaucoma in both first and second generation relatives of those affected as compared to relatives in the control group. When compared with other epidemiologic studies, such as an analysis of first-degree relatives of patients from the Rotterdam study, which showed a PAR of 16%, our study actually demonstrates a greater familial contribution to glaucoma. The UPDB is a valuable and unique resource providing a large population from which to analyze the familial risk of glaucoma

SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma

Purpose: To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG). Methods: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts. Results: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, $p_{rec}$=0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG ($p_{dom}$=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028). Conclusions: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association