Ambient Air Pollution and the Risk of Central Retinal Artery Occlusion.

PURPOSE: To investigate whether daily changes in ambient air pollution were associated with an increased risk of central retinal artery occlusion (CRAO). DESIGN: Retrospective population-based cohort study. PARTICIPANTS: We identified patients newly diagnosed with CRAO between 2001 and 2013 in a representative database of 1 000 000 patients that were randomly selected from all registered beneficiaries of the National Health Insurance program in Taiwan. We identified air pollutant monitoring stations located near these patients' residences in different administrative areas in Taiwan to determine the recorded concentrations of particulate matter ≤2.5 µm (PM2.5), particulate matter ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3). Patients without corresponding monitoring stations were excluded. METHODS: We used a time-stratified case-crossover study design and conditional logistic regression analysis to assess associations between the risk of CRAO and the air pollutant levels in the days preceding each event. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We enrolled 96 patients with CRAO in this study. The mean age was 65.6 years (standard deviation, 12.7 years) and 67.7% of patients were male. The risk of CRAO onset was significantly increased (OR, 1.09; 95% CI, 1.01-1.17; P = 0.03) during a 5-day period following a 1 part per billion increase in NO2 levels. After multipollutant adjustment, the increase in risk was most prominent after 4 days (OR, 1.40; 95% CI, 1.05-1.87; P = 0.02) to 5 days (OR, 2.16; 95% CI, 1.10-4.23; P = 0.03) of elevated NO2 levels in diabetic patients. The risk of CRAO onset also significantly increased in patients with hypertension and in patients ≥65 years old, after 1 day of elevated SO2 levels (OR, 1.88; 95% CI, 1.07-3.29; P = 0.03 and OR, 1.90; 95% CI, 1.13-3.21; P = 0.02, respectively). The transient concentration of the other air pollutants, including PM2.5, PM10, and O3, did not significantly affect the occurrence of CRAO in this study. CONCLUSIONS: These results demonstrated a positive association between air pollution and CRAO onset, particularly in patients with diabetes or hypertension and those older than 65 years.

Amiodarone-Associated Optic Neuropathy: A Nationwide Study.

PURPOSE: To investigate whether amiodarone use is associated with an increased risk of optic neuropathy. DESIGN: Retrospective population-based cohort study. PARTICIPANTS: Patients newly treated with amiodarone between 2005 and 2009 were identified from the Taiwan National Health Insurance Research Database. For each case patient, the study also included 4 age- and gender-matched control subjects who did not receive amiodarone treatment. METHODS: Cox multivariate regression analysis was used to assess the association between amiodarone and the occurrence of optic neuropathy. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The analysis included 6175 amiodarone-treated patients and 24 700 controls. The mean age was 66.7 years and 55.3% of subjects were male. The mean follow-up was 688 days. During the observational period, optic neuropathy developed in 17 amiodarone-treated patients (0.3%) and 30 control patients (0.1%; P = 0.006). Multivariate Cox regression analysis showed that amiodarone-treated patients had a 2-fold increased risk of optic neuropathy (HR, 2.09; 95% CI, 1.13-3.85; P = 0.02). After stratification by gender, amiodarone use remained a significant factor for optic neuropathy development among male subjects (HR, 3.05; 95% CI, 1.42-6.55; P = 0.004), but not among female subjects (HR, 1.15; 95% CI, 0.38-3.47; P = 0.81). Among amiodarone-treated patients, male gender was associated with a nearly 3-fold increased risk of optic neuropathy development compared with female gender (HR, 2.91; 95% CI, 0.94-9.01; P = 0.06). We also detected a trend of increased cumulative incidence of optic neuropathy with longer treatment duration (>41 vs. ≤41 days; HR, 3.46; 95% CI, 0.99-12.07; P = 0.05). However, higher daily dose did not increase the risk of optic neuropathy (HR, 0.96; 95% CI, 0.91-1.00; P = 0.07). CONCLUSIONS: These results demonstrated a higher risk of optic neuropathy in patients treated with amiodarone, especially in males and possibly in patients with longer duration of treatment.

"Seeing but not identifying": pure alexia coincident with prosopagnosia in occipital arteriovenous malformation.

BACKGROUND: Pure alexia and prosopagnosia are two separate and uncommon disorders of visual recognition in neuro-ophthalmology. We report an extremely rare case of pure alexia coincident with prosopagnosia secondary to occipital arteriovenous malformation. The manifestations of these two visual recognition disorders are also described. METHODS: A 35-year-old, left-handed women had suffered from severe blurred vision when recognizing her family's faces and was unable to read or associate separate parts of a word into a whole word. Her visual field revealed slight right homonymous hemianopia. Computed tomography scans and magnetic resonance images were arranged and vertebral angiography confirmed the diagnosis of left occipital arteriovenous malformation. RESULTS: Gamma-knife stereoscopic radiotherapy was performed. Two months after the treatment, the ability to recognize faces and read improved and the visual field recovered. CONCLUSIONS: Ophthalmologists should keep in mind that usual complaints of "blurred vision" might correlate with unusual visual recognition disorders. Pure alexia and prosopagnosia have not been reported to occur together and the left-handed- dominance in our case leads to this scarce concurrence.

Short-term effect of atropine on higher-order aberrations in myopic children.

BACKGROUND: This study aimed to investigate the short-term effect of cycloplegia on higher-order aberrations (HOAs) in school-age myopic children who received 0.25% atropine for cycloplegic refraction. METHODS: We performed a retrospective chart review of 24 myopic children between the ages of 5 and 15 years, who had received one topical drop of 0.25% atropine for three consecutive nights before undergoing cycloplegic refraction. Auto-refraction, visual acuity, and HOAs measured with the iTrace aberrometer were compared before and after atropine use. To account for the effect of cycloplegia, the amount of HOAs under matching scanning sizes was compared. RESULTS: There were statistically significant differences in the spherical equivalent, with a hyperopic shift after atropine use (p < 0.001). Corrected visual acuity and spherical aberrations showed no significant change under the respective pupil and scanning sizes before and after atropine use. Under identical scanning sizes, there was a significant change in total spherical aberration (from 0.03 to 0.06 µm, p = 0.044) and internal spherical aberration (from -0.10 to -0.05 µm, p = 0.049) after atropine use. Differences in corneal spherical aberration were insignificant. CONCLUSION: The positive shift of spherical aberration induced by the inhibition of accommodation in myopic children may have a possible effect against myopic progression. Future studies can focus on the long-term effect on HOAs and impact on visual quality with lower concentrations of atropine.

Novel mutations of the OPA1 gene in Chinese dominant optic atrophy.

PURPOSE: To investigate OPA1 gene mutations in Chinese patients with autosomal dominant optic atrophy and sporadic optic atrophy. DESIGN: Molecular genetic studies and observational case series. PARTICIPANTS: Twenty-four patients from 10 unrelated Chinese pedigrees of autosomal-dominant optic atrophy, 35 isolated cases with bilateral optic atrophy of unknown cause, and 50 unrelated normal controls. METHODS: Genomic DNA was extracted from peripheral blood leukocytes. All 28 coding exons of the OPA1 gene and flanking intron splice sites were sequenced. Putative mutations were reexamined for segregation in the respective families by direct sequencing. Further characterization of selected splicing site mutations was performed by reverse transcription-polymerase chain reaction (PCR) of each patient's leukocyte mRNA. MAIN OUTCOME MEASURES: Direct sequencing of the OPA1 gene. RESULTS: Four OPA1 gene mutations were detected, including 2 splicing site mutations (c.1065+2T>C on intron 10 and c.1212+2insT on intron 12), 1 deletion (c.1776_1778delACT on exon 19), and 1 missense mutation (c.2846 T>C on exon 28). The c.1212+2insT, c.1776_1778delACT, and c.2846T>C mutations were newly identified OPA1 mutations. Reverse transcription (RT)-PCR and direct sequencing revealed that the splicing site mutations on c.1065+2T>C and c.1212+2insT caused skipping of exons 10 and 12, respectively. The c.1776_1778delACT mutation led to a deletion of the Leu amino acid on residue 593. OPA1 mutations were found in 4 of 10 familial cases (40 %) and in 1 of 35 sporadic cases of optic atrophy. CONCLUSIONS: OPA1 gene mutations are causative in Chinese autosomal-dominant optic atrophy and sporadic optic atrophy. Screening for OPA1 gene mutations in patients with childhood onset optic atrophy who have no affected relatives is useful in making the diagnosis.

Reflux of jugular and retrobulbar venous flow in transient monocular blindness.

OBJECTIVE: Transient monocular blindness (TMB) attacks may occur during straining activities that impede cerebral venous return. Disturbance of cerebral and orbital venous circulation may be involved in TMB. METHODS: Duplex ultrasonography and Doppler-flow measurement of jugular and retrobulbar veins were performed in 134 consecutive patients with TMB and 134 age- and sex-matched control subjects. All recruited patients received thorough examinations to screen for possible underlying causes. RESULTS: Of the 134 patients with TMB, 48 patients had ipsilateral carotid arterial lesion and 7 patients had TMB attack(s) caused by cardiac embolism. Of the remaining 79 patients with undetermined cause, 46 had 3 or more TMB attacks (undetermined-frequent group) and 33 had fewer than 3 attacks. In comparison with the control subjects, the TMB patients had greater frequencies of jugular venous reflux (57 vs 30%; p < 0.0001; odds ratio [OR]: 3.079, 95% confidence intervals [CI]: 1.861-5.096) and flow reversal in the superior ophthalmic vein (RSOV; 37 vs 9%; p < 0.0001; OR: 6.052, CI: 3.040-12.048). The undetermined-frequent group had the greatest frequencies of jugular venous reflux (74%, 34 patients; OR: 6.66, CI: 3.13-14.17) and RSOV (59%, 27 patients; OR: 6.51, CI: 3.12-13.58). Of the 50 patients with RSOV, 47 (94%) had RSOV on the side of the TMB attacks. INTERPRETATION: The increased incidences of jugular and orbital venous reflux in TMB patients suggest that disturbance of cerebral and orbital venous circulation is involved in the pathogenesis of TMB, especially among patients with frequent attacks of undetermined cause.

Altered retrobulbar hemodynamics in patients who have transient monocular blindness without carotid stenosis.

BACKGROUND AND PURPOSE: This study was to evaluate the retrobulbar hemodynamics in patients who have transient monocular blindness (TMB) without carotid stenosis. METHODS: Fifty-nine patients who have TMB without carotid stenosis were studied along with 59 age- and sex-matched controls. Color Doppler-imaging was used to study the retrobulbar hemodynamic by measuring the flow velocities (peak-systolic velocity, and end-diastolic velocity), vascular resistance indices (pulsatility index, and resistance index) in central retinal arteries, short posterior ciliary arteries, and ophthalmic arteries. The patients were divided into 2 groups according to the attack frequency: group 1 (occasional TMB, 2 or fewer attacks, 26 patients) and group 2 (frequent TMB, 3 or more attacks, 33 patients). RESULTS: The risk factors for atherosclerosis were similar between the cases and controls. The means of end-diastolic velocity were significantly lower in central retinal arteries and ophthalmic arteries, and the pulsatility index and resistance index were significantly higher in all the 3 retrobulbar vessels in TMB patients than for the controls. The differences between patients and controls were greater for the group-2 patients. CONCLUSIONS: Patients who have TMB without carotid stenosis had altered retrobulbar hemodynamics with a generalized increase in vascular resistance in the retrobulbar arteries. The role of venous hypertension as an etiology needs further study.

Leber's hereditary optic neuropathy: a multifactorial disease.

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease characterized by acute or subacute visual loss predominantly affecting young men. The majority of LHON cases are caused by one of the three primary mitochondrial DNA (mtDNA) mutations: G3460A/ND1, G11778A/ND4, or T14484C/ND6. Although the primary etiological factor of LHON is a mtDNA mutation, the presence of a primary mtDNA mutation does not necessarily lead to visual loss. The pathogenesis of LHON remains unclear. The marked incomplete penetrance and gender bias indicate that additional genetic (nuclear or mitochondrial) and epigenetic factors may also be involved. Deficiency in respiratory chain function and reactive oxygen species (ROS) are believed to play a pivotal role in the pathophysiology of the disease.

Association of the Y402H polymorphism in complement factor H gene and neovascular age-related macular degeneration in Chinese patients.

PURPOSE: Age-related macular degeneration (AMD), with its complex traits and multiple risk factors, is the leading cause of blindness in the elderly. A strong association between a coding variant, Y402H, in the complement factor H gene (CFH) and AMD has been recently identified in white patients. This study was conducted to investigate the association between the Y402H polymorphism in CFH and neovascular AMD in Chinese patients. METHODS: One hundred sixty-three Chinese patients with neovascular AMD and 232 age-matched healthy controls were enrolled in the study. Genomic DNA from white blood cells was extracted. The Y402H polymorphism in CFH, with the substitution of T to C at nucleotide position 1277 in exon 9, was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The association between the genetic polymorphism and the disease was examined by chi(2) test and logistic regression. RESULTS: The frequency of the risk allele, 1277C, was 11.3% in AMD patients compared with 2.8% in controls (P < 0.00001). Genotype frequency differed significantly between the two groups (1277TT 81.0%, 1277TC 15.3%, and 1277CC 3.7% in the AMD group; 1277TT 94.4%, 1277TC 5.6%, and 1277CC 0% in the control group; P < 0.0001). The 1277C allele significantly increased the risk for neovascular AMD and had an odds ratio of 4.4 (95% confidence interval [95% CI], 2.3-8.5; P < 0.00001). CONCLUSIONS: The allele frequency of Y402H polymorphism in CFH has an ethnic variation, with much lower 1277C frequency in Chinese than in white patients. Despite this, the polymorphism is significantly associated with neovascular AMD in the Chinese population.

Induction of vitronectin and integrin alphav in the retina after optic nerve injury.

PURPOSE: Vitronectin is a secreted glycoprotein present in blood plasma and is present in the extracellular matrix of many tissues. It was found in the retinal cDNA library that contains genes whose expression is upregulated after optic nerve injury in a previous study. The purpose of this study was to assess the temporal and spatial changes in expression of vitronectin and integrin alphav in the retina following optic nerve injury. METHODS: Adult Balb/c mice underwent crush of the optic nerve in one eye only. RT-PCR was used to determine the temporal expression of vitronectin mRNA in the retina after injury. In addition, expression at the protein level in the retina and the optic nerve of vitronectin and its major receptor subunit, integrin alphav, was analyzed by immunohistochemistry. RESULTS: Upregulation of vitronectin mRNA in the retina was detected at one day after injury, peaking at three days, and maintained up to one week. An elevated expression of vitronectin protein was also observed in the inner retina, optic nerve head, and the optic nerve after nerve crush. In the inner retina, the increased expression of vitronectin was found in retinal ganglion cells (RGCs) and its surrounding extracellular matrix. Expression of integrin alphav was also increased in the RGC layer and in the glial cells of the nerve head and the crush site. CONCLUSIONS: As vitronectin is an extracellular protein that can support cell attachment and promote neurite extension, elevated expression of vitronectin and its receptor may facilitate axonal regeneration following injury. We propose that treatment sustaining secretion of endogenous vitronectin or direct application of exogenous vitronectin may be a method to augment regeneration of the severed optic axons.

Early relapse in multiple sclerosis-associated optic neuritis following the use of interferon beta-1a in Chinese patients.

PURPOSE: The incidence of multiple sclerosis (MS) is relatively rare in Chinese. The beneficial effect of interferon beta-1a in modifying the disease course of MS has been rarely analyzed in Chinese patients. The aim of this study was to investigate the clinical response to interferon beta1-a in Chinese patients with MS-associated optic neuritis (ON). METHODS: A retrospective case control study was conducted in 20 MS patients with optic nerve involvement. The interferon (IF) group comprised ten patients receiving interferon beta-1a. The noninterferon (NIF) group comprised another ten MS patients with optic nerve involvement who did not receive interferon treatment. The clinical characteristics, laboratory data, management, and disease course were retrospectively analyzed. The main outcomes of the study were the annualized relapse rate (ARR) for MS, and final visual outcome data. RESULTS: The ARR did not differ between the pretreatment period and the posttreatment period within the IF group. There was also no significant decrease of ARR in the IF group when compared with the NIF group. However, we observed an early recurrence of ON in 50% of the IF cases following the use of interferon beta-1a. The final visual outcome did not differ between the IF group and the NIF group. CONCLUSIONS: The use of interferon beta-1a should be carefully monitored because early relapse of ON may complicate the treatment course in this patient group.

Low conversion rate to multiple sclerosis in idiopathic optic neuritis patients in Taiwan.

PURPOSE: To investigate the clinical characteristics of patients with idiopathic optic neuritis (ON) in Taiwan and to assess the conversion rate to multiple sclerosis (MS) in these patients. METHODS: We studied the medical records of a total of 109 patients with a clinical diagnosis of idiopathic ON treated in the Taipei Veterans General Hospital during the period from January 1986 to May 2003. Clinical characteristics, management, and disease courses were retrospectively reviewed. Our main focus was on the development of multiple sclerosis after an ON attack. Univariate and multivariate analyses were used to evaluate the risk indicators for MS conversion. RESULTS: The patients (58 women, 51 men) had a mean age of 41.2 years at onset. ON was retrobulbar in 46.8% of the patients. Management with or without pulse therapy did not affect the final visual outcome. Female sex, retrobulbar type ON, recurrent cases, elevated cerebrospinal fluid (CSF) IgG index, and central nervous system (CNS) imaging abnormalities were identified as risk indicators for the development of MS (P < 0.05). The 2-year cumulative probability of developing MS was 5.92%, and the 5-year cumulative probability was 14.28%. The conversion rate to MS did not differ among treatment groups. CONCLUSIONS: Idiopathic ON patients in Taiwan have an older age at onset and a higher percentage of optic disc edema than reported in previous literature. The characteristic features of ON patients associated with a high risk of developing MS are female sex, retrobulbar type ON, CNS imaging abnormalities, elevated CSF IgG index, and recurrence. Idiopathic ON patients in Taiwan display a significantly lower conversion rate to MS.

Neuroimaging and clinical features of patients with optic nerve hypoplasia in Taiwan.

PURPOSE: To investigate the clinical and neuroradiographic features of Chinese patients with optic nerve hypoplasia (ONH). METHODS: This was a retrospective case series study. The medical records and magnetic resonance imaging (MRI) studies of patients diagnosed with ONH from September 2001 to December 2013 in the neuro-ophthalmology clinic of Taipei Veterans General Hospital were reviewed. RESULTS: A total of eight eyes of five patients with ONH were enrolled in this study (1 male, 4 females). The mean age at diagnosis was 14.5 ± 12.0 years (range 0.25-30 years). Ocular examination revealed approximately half of the eyes had tortuous retinal vessels. In MRI studies, all patients had midline brain abnormalities including ectopic posterior pituitary gland (60%), agenesis of septum pellucidum (20%), and Rathke's cleft cyst (20%). Two patients had endocrinopathies-one suffered from hypopituitarism and the other had hyperprolactinemia. Both of them showed ocular findings of tortuous retinal vessels. CONCLUSION: A high prevalence of midline brain abnormalities was noted in ONH patients of Chinese ethnicity. The presence of tortuous retinal vessels in patients with a midline brain anomaly may indicate the occurrence of endocrinopathy.

Changes in Mitochondrial Morphology and Bioenergetics in Human Lymphoblastoid Cells With Four Novel OPA1 Mutations.

PURPOSE: Mutations in the optic atrophy 1 gene (OPA1) have been reported in patients with autosomal dominant optic atrophy (ADOA). OPA1 plays important roles in mitochondrial dynamics and cell apoptosis. The link between OPA1 mutations and changes in bioenergetics is still not fully resolved. The aim of this study was to investigate the effects of OPA1 mutations on the mitochondrial tubular network and bioenergetics. METHODS: We established lymphoblastoid cell lines from four ADOA families harboring different OPA1 mutations, unaffected relatives (internal control cell lines), and unrelated normal controls (normal control cell lines). OPA1 splice variants and mRNA were analyzed by reverse transcription-PCR and quantitative real-time PCR. Protein isoforms were examined by Western blotting. The mitochondrial network was visualized by confocal microscopy. Mitochondrial bioenergetics were assessed using a Seahorse XF24 flux analyzer. Mitochondrial membrane potential and oxidative damage were analyzed by flow cytometry. RESULTS: OPA1 mutant cell lines showed significant decreases in OPA1 mRNA and protein expression, mitochondrial membrane potential, and ATP synthesis. A marked deficiency of the long isoform of OPA1 was observed in cells with OPA1 mutations in the middle domain and GTPase effector domain. Confocal microscopy revealed increased mitochondrial fragmentation in OPA1 mutant cells. OPA1 mutant cells also displayed reduced oxygen consumption and underwent glycolysis to produce ATP. Moreover, OPA1 mutations caused the accumulation of oxidative damage. CONCLUSIONS: Our experiments demonstrated that OPA1 mutations induced mitochondrial fragmentation, uncoupled mitochondrial respiration, and elicited dysfunctional bioenergetics. However, there were no significant differences among the various OPA1 mutations.

Retinal nerve fiber layer thickness in unilateral amblyopia.

PURPOSE: To test the hypothesis that eyes with amblyopia may have thicker retina, retinal nerve fiber layer thickness (RNFLT) was investigated in patients with unilateral amblyopia. METHODS: Thirty-eight patients with unilateral amblyopia were studied. Among them, 20 patients had amblyopia with strabismus and 18 had refractive amblyopia without strabismus. Nineteen of 38 had anisometropia of 2.0 D or more. In addition, 17 patients with anisometropia of 2.0 D or more but without amblyopia were enrolled as control subjects. RNFLT was measured by optical coherence tomography with scan pattern "Nerve Head 2.0R" (Carl Zeiss Meditec, Dublin, CA). Average RNFLT was multiplied with their corresponding scan circumferences to estimate the integral values of the total RNFL area (RNFLT(estimated integrals)). RESULTS: In all 38 patients with unilateral amblyopia, the difference in RNFLT and in RNFLT(estimated integrals) between the amblyopic eyes and the normal fellow eyes were statistically significant. Multivariate regression analysis with adjustment for axial length, spherical equivalence, age, and sex indicated significant differences as well. In the group of strabismic amblyopia, the difference in RNFLT and in RNFLT(estimated integrals) between the amblyopic eyes and the normal fellow eyes did not reach statistical significance. However, in the group of refractive amblyopia, the difference in RNFLT and in RNFLT(estimated integrals) between the amblyopia eyes and the normal fellow eyes both had a statistical significance. In the 19 patients with anisometropic amblyopia, the difference in RNFLT and in RNFLT(estimated integrals) between the amblyopic eyes and the normal fellow eyes were statistically significant. In the control group of 17 patients with nonamblyopic anisometropia, the difference in RNFLT and in RNFLT(estimated integrals) between both eyes did not reach statistical significance. CONCLUSIONS: RNFLT may be affected by refractive amblyopia, but further histopathologic confirmation is needed.

Association of ocular dominance and anisometropic myopia.

PURPOSE: To determine the association between ocular dominance and degree of myopia in patients with anisometropia. METHODS: Fifty-five subjects with anisometropic myopia were recruited. None of them had amblyopia. Refractive error and axial length were measured in each subject. Ocular dominance was determined using the hole-in-the-card test and convergence near-point test. RESULTS: There was a threshold level of anisometropia (1.75 D) beyond which the dominant eye was always more myopic than the nondominant eye. Of the 33 subjects with anisometropia of < or =1.75 D, the dominant eye was more myopic in 17 (51.5%) subjects. Dominant eyes, determined by the hole-in-the-card test, had a significantly greater myopic spherical equivalent (-5.27 +/- 2.45 D) than nondominant eyes (-3.94 +/- 3.10 D; P < 0.001). Dominant eyes also had a longer axial length than nondominant eyes (25.15 +/- 0.96 mm vs. 24.69 +/- 1.17 mm, respectively; P < 0.001). The difference was more evident in those subjects with higher anisometropia (>1.75 D), but was not significant in those with lower anisometropia (< or =1.75 D). Similar results were obtained using the convergence near-point test. CONCLUSIONS: The present study shows that the dominant eye has a greater degree of myopia than the nondominant eye in subjects with anisometropic myopia. Taking ocular dominance into account in the design of randomized clinical trails to assess the efficacy of myopia interventions may provide useful information.

Increased 8-hydroxy-2'-deoxyguanosine in leukocyte DNA in Leber's hereditary optic neuropathy.

PURPOSE: This study was conducted to test the hypothesis that oxidative stress is involved in the pathogenesis of Leber's hereditary optic neuropathy (LHON). The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized DNA base common in cells undergoing oxidative stress, was measured in leukocyte DNA from patients with LHON and normal control subjects. METHODS: The 8-OHdG and deoxyguanosine (dG) content in leukocyte DNA from 25 patients with LHON with an 11778 mitochondrial (mt)DNA mutation, 14 asymptomatic maternal relatives, and 27 unrelated normal control subjects were measured using high-performance liquid chromatography and electrochemical detection methods. RESULTS: The mean 8-OHdG/10(5) dG ratio from leukocyte DNA was 1.34 +/- 0.99 in patients with LHON, 1.00 +/- 0.91 in their asymptomatic maternal relatives, and 0.31 +/- 0.20 in normal control subjects, respectively. There was a statistically significant difference in the mean 8-OHdG/10(5) dG ratio between patients with LHON and normal control subjects and between asymptomatic maternal relatives and normal control subjects. The difference between patients with LHON and asymptomatic maternal relatives did not reach statistical significance. CONCLUSIONS: Patients with LHON with an 11778 mtDNA mutation had higher oxidative DNA damage. Oxidative stress has a key role in the pathogenesis of LHON.

Change of gene expression profiles in the retina following optic nerve injury.

The purpose of the present study was to search for changes in gene expression patterns in the retina following optic nerve injury. We conducted a subtractive hybridization for comparison of the mRNAs in those retinas receiving optic nerve crush injury and those receiving sham operation. Both forward and reverse subtractions were carried out for 8-h and 24-h time points postoperatively. Resultant subtractive cDNA for each group was re-amplified and cloned to a plasmid. After DNA sequencing, the identity of subtractive cDNA was analyzed by blasting sequences to the Nonredundant gene database, Unigene database, and dbest database at NCBI. Thirty-four known genes and 32 EST were found in the forward subtractions. Forty-two known genes and 46 EST were found in reverse subtractions. Identities of the rest could not been found in the databases. To verify the subtractive results, RT-PCR was performed to test expression patterns of eight known genes found in the above analysis. Among these eight genes, seven demonstrated a statistically significant difference between the crushed eyes and the control eyes by quantitative image analysis. Together, our data show that expression of fatso, ephrin B2, NonO, Zfx, vitronectin, and XLRS increased after optic nerve injury, and expression of stathmin exhibited reduction after injury.