Xinghuai Sun

Bioactive natural products from endophytes: A review

Endophytes, microorganisms that reside in the internal tissues of living plants without causing any immediate overt negative effects, have been found in every plant species examined to date and recognized as potential sources of novel natural products for exploitation in medicine, agriculture, and industry with more and more bioactive natural products isolated from the microorganisms. In this review, we focus mainly on bioactive natural products from endophytic microorganisms by their different functional roles. The prospect and facing problems of isolating natural products from endophytes are also discussed.

Correlation between optic disc perfusion and glaucomatous severity in patients with open-angle glaucoma: an optical coherence tomography angiography study

PurposeTo explore how optic disc perfusion varies in patients with open-angle glaucoma (OAG) and how this correlates with glaucoma severity.MethodsWe performed a prospective and cross-sectional observational study that included 62 eyes from 62 patients with OAG, divided into three groups according to their visual field (VF) results, and 20 eyes from 20 normal control subjects. Optic disc perfusion was studied using optical coherence tomography angiography (angio-OCT), and flow index and vessel density were determined. The VF, mean deviation (MD), pattern standard deviation (PSD), retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness were also recorded. The potential associations between disc perfusion and VF defects or structural loss were analyzed.ResultsIn OAG patients, the disc flow index and vessel density were significantly lower than in normal controls (all p<0.001) and were correlated with the severity of glaucoma. In OAG eyes, the flow index and vessel density were significantly correlated with MD, RNFL, and GCC thickness (all p<0.01), but were not in the normal controls. The receiver operating characteristic (ROC) curve analysis also revealed that disc flow index and vessel density had the power to differentiate normal eyes from eyes with OAG (under the ROC curves: 0.82 and 0.80, respectively).ConclusionsAngiograms demonstrated a reduced disc flow index and vessel density in glaucoma, and this reduction was closely related to GCC thickness. This indicated that measurement of disc perfusion by angio-OCT might be important for the monitoring of glaucoma.

Parapapillary Atrophy: Histological Gamma Zone and Delta Zone

Background To examine histomorphometrically the parapapillary region in human eyes. Methodology/Principal Findings The histomorphometric study included 65 human globes (axial length:21–37 mm). On anterior-posterior histological sections, we measured the distance Bruchs membrane end (BME)-optic nerve margin (“Gamma zone”), BME-retinal pigment epithelium (RPE) (“Beta zone”), BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. “Delta zone” was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm) was significantly (P = 0.01) larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28) associated with axial length. Beta zone was significantly (P = 0.004) larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm) was associated with axial length (P<0.001;r2 = 0.73) with an increase starting at an axial length of 26.5 mm. It was not significantly (P = 0.24) associated with glaucomatous optic neuropathy. Delta zone (present only in eyes with axial length of ≥27 mm) was associated with axial length (P = 0.001) and scleral flange length (P<0.001) but not with glaucoma (P = 0.73). Conclusions/Significance Parapapillary gamma zone (peripapillary sclera without overlying choroid, Bruchs membrane and deep retinal layers) was related with axial globe elongation and was independent of glaucoma. Delta zone (no blood vessels >50 µm diameter within gamma zone) was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruchs membrane without RPE) was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure.

A new tonometer--the Corvis ST tonometer: clinical comparison with noncontact and Goldmann applanation tonometers.

PURPOSE To compare intraocular pressure (IOP) measurements obtained using the Topocon noncontact tonometer (NCT), the Goldmann applanation tonometer (GAT), and the Corvis ST (CST), a newly developed tonometer with features of visualization and measurement of the corneal deformation response to an air impulse. A secondary objective was to assess the agreement among the devices. METHODS Fifty-nine participants, including glaucoma patients (36 cases) and control volunteers (23 cases), were enrolled. One eye was selected randomly for further study. IOP measurements were obtained with the CST, NCT, and GAT by two experienced clinicians. IOP values were compared. Intraobserver variability and interobserver variability were assessed by the coefficient of variation and intraclass correlation coefficient. Device agreement was calculated by Bland-Altman analysis. RESULTS Mean IOP for all examined eyes was 18.9 ± 5.8 mm Hg for CST, 21.3 ± 6.8 mm Hg for NCT, and 20.3 ± 5.7 mm Hg for GAT. There was no statistically significant difference in IOP measurements among the tonometers except between the CST and NCT. Correlation analysis showed a high correlation between each pair of devices (all P < 0.001). The CST displayed the best intraobserver variability and interobserver variability. Bland-Altman analysis revealed a bias between CST and GAT, CST and NCT, and GAT and NCT of -1.3, -2.4, and -1.1 mm Hg, with 95% limits of agreement of -6.2 to 3.5 mm Hg, -10.1 to 5.2 mm Hg, and -8.3 to 6.2 mm Hg, respectively. CONCLUSIONS The CST offers an alternative method for measuring IOP. IOP measurements taken with these devices may not be interchangeable.

Anxiety and Depression in Patients with Dry Eye Syndrome

Purpose: This study aimed to determine whether patients with dry eye syndrome [DES] have more symptoms of anxiety and depression than controls without DES. Methods: In this case-control study, the sample consisted of 89 DES subjects (13 diagnosed with Sjögren’s syndrome [SS]) and 73 control subjects. Each subject was diagnosed as having DES or was chosen as a control subject by an ophthalmologist. The Zung Self Rating Anxiety Scales (SAS), Zung Self Rating Depression Scales (SDS), and Ocular Surface Disease Index (OSDI) were administered to all subjects. Scores of SAS and SDS, measuring level of anxiety and depression symptoms, were compared between the DES group and the control group. Correlations with other health status measures were conducted. Results: The SAS and SDS scores of the DES group were significantly higher than the control group (P < 0.001, P < 0.001). The prevalence of DES subjects with anxiety or depression symptoms was significantly higher than in the control group (P = 0.003, P < 0.001). In the DES group, SAS scores were found to be correlated with OSDI and educational level. SDS scores were found to be correlated with OSDI. Neither SAS nor SDS scores were correlated with age, sex, household income, tear break up time (BUT), Schirmer Test 1 (S1T), corneal fluorescein staining (FL), or visual acuity. Conclusion: Anxiety and depression are correlated with DES, demonstrating that DES is an important public health problem that merits increased attention and research.

Macular Perfusion in Healthy Chinese: An Optical Coherence Tomography Angiogram Study

PURPOSE To investigate macular perfusion in healthy Chinese individuals and examine its dependence on age and sex. METHODS Healthy adult Chinese individuals were recruited. Macular perfusion was measured by spectral-domain optical coherence tomography (OCT) using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. The parafoveal flow index and vessel area density as well as the area of the foveal capillary-free zone (CFZ) were quantified. RESULTS A total of 76 eyes in 45 subjects were included (20 males and 25 females, mean age 36 ± 11 years). The mean parafoveal flow index was 0.099 ± 0.013; the mean vessel area density was 0.891 ± 0.073; and the mean CFZ area was 0.474 ± 0.172 mm2. All three parameters were significantly correlated with age (flow index: P = 0.00; vessel area density: P = 0.00; CFZ area: P = 0.02). The flow index and vessel area density decreased annually by 0.6% and 0.4%, respectively, and CFZ area increased by 1.48% annually. The CFZ area was larger in females than in males, while all three parameters seemed to change more rapidly with age in males than in females. CONCLUSIONS In healthy Chinese eyes, macular perfusion decreased with increasing age, and decreased more rapidly in males than in females. The application of OCT angiograms may provide a useful approach for monitoring macular perfusion, although caution must be exercised with regard to age- and sex-related variations.

Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma

We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10−8) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10−6). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10−19 for rs2487032 representing ABCA1 and P = 5.77 × 10−10 for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.

Microstructure of parapapillary atrophy: beta zone and gamma zone.

PURPOSE To examine the morphologic features of parapapillary atrophy by using enhanced depth imaging optical coherence tomography (EDI-OCT) and color fundus photographs. METHODS The clinical observational comparative study included 80 normal eyes of 46 subjects and 80 eyes of 46 patients with primary open-angle glaucoma. Both groups did not vary significantly in axial length (P = 0.62) and refractive error (P = 0.30). Color fundus photographs and cross-sectional B-scan images obtained by EDI-OCT were examined. On the EDI-OCT images, we measured a gamma zone defined as the region between the temporal disc margin to the beginning of Bruchs membrane, and a beta zone defined as Bruchs membrane without retinal pigment epithelium. RESULTS The gamma zone (mean area: 1.13 ± 2.04 mm(2)) was significantly associated with longer axial length (P < 0.001; standardized coefficient beta: 0.48), longer vertical disc diameter (P < 0.001; beta: 0.43), older age (P = 0.008; beta: 0.22), and the absence of glaucoma (P = 0.03; beta: -0.19). The beta zone (mean area: 0.85 ± 0.60 mm(2)) was associated with longer axial length (P < 0.001; beta: 0.39) and the presence of glaucoma (P < 0.001; beta: 0.48). CONCLUSIONS In addition to associations with older age, increasing myopia, and larger disc size, the EDI-OCT-defined gamma zone of parapapillary atrophy was associated with the absence of glaucoma, whereas the EDI-OCT-defined beta zone was associated with the presence of glaucoma. Differentiation between the beta zone and the gamma zone may be clinically useful.

Assessment of tear film stability in dry eye with a newly developed keratograph.

Purpose: To investigate the applicability of a newly developed corneal topographer in assessing tear film stability. Methods: This is a prospective, case–control study. Forty-four Chinese dry eye patients and 41 normal subjects were recruited. Noninvasive tear film break-up time (NI-BUT) was measured using a new method based on a corneal topographer equipped with modified scan software. The reliability of the measurements was determined. Then, the correlations between the NI-BUT and the traditional fluorescein tear film break-up time, Schirmer I test values, and inferior tear meniscus height measurements were determined. The receiver operating characteristic curve technique was used to evaluate the NI-BUT examination in the diagnosis of dry eye. Results: In total, a significant difference between the NI-BUT and the fluorescein tear film break-up time was found (3.2 ± 2.3 seconds vs. 5.2 ± 3.4 seconds; P < 0.001). The coefficient of variation and intraclass correlation coefficient values of NI-BUT were 12.8% and 0.93, respectively, for NI-BUT for intraobserver repeatability and 15.4% and 0.88, respectively for interobserver repeatability. The NI-BUT showed a good correlation with other dry eye examinations (all P < 0.05). In addition, the NI-BUT was significantly shorter in dry eye patients (2.0 ± 0.2 seconds) than in normal subjects (4.3 ± 0.3 seconds; P < 0.001). When the cutoff value was set at <2.65 seconds, the sensitivity and specificity of the test were 84.1% and 75.6%, respectively. Conclusions: Measurements of NI-BUT obtained with the newly developed corneal topographer may provide a simple, noninvasive screening test for dry eyes with acceptable sensitivity, specificity, and repeatability.

Screening of taxol-producing endophytic fungi from Taxus chinensis var. mairei

A total of 38 endophytic fungus strains were isolated from Taxus chinensis var. mairei by the aseptic technique. Genomic DNA was extracted from isolated endophytic fungi and subjected to polymerase chain reaction (PCR) analysis for the presence of the Taxus taxadiene synthase (TS) gene, a rate-limiting enzyme gene in the taxol biosynthetic pathway. Twelve out of 38 isolated endophytic fungus strains showed PCR positive for the ts gene. Subsequently, taxol and its related compounds were extracted from culture filtrates and mycelia of the PCR positive strains, separated by column chromatography, and analyzed by High Performance Liquid Chromatography and Mass Spectrum. The analysis result showed that 3 strains could produce taxol and its related compounds at the detectible level. This study indicates that molecular detection of the ts gene is an efficient method for primary screening of taxol or its related compound-producing endophytic fungi, which can improve prominently screening efficiency.