Yongxiang Jiang

Changes in corneal astigmatism and high order aberrations after clear corneal tunnel phacoemulsification guided by corneal topography.

PURPOSE To study changes in corneal astigmatism and high order aberrations after clear corneal tunnel phacoemulsification guided by corneal topography. METHODS All patients were randomly assigned to the test group or the control group. Corneal topography-guided clear corneal tunnel phacoemulsification followed by intraocular lens (IOL) implantation was performed on 22 eyes of 16 patients in the test group and conventional temporal corneal tunnel phacoemulsification and IOL implantation were performed on 22 eyes of 21 patients in the control group. The corneal astigmatism and high order aberrations were measured using the NIDEK OPD-Scan aberrometer and topographer preoperatively and up to 3 months after surgery. The corneal astigmatism and sixth order root-mean-square (RMS) for corneal coma, trefoil, spherical, secondary coma, and secondary spherical aberrations at 4-mm pupil diameters were compared. RESULTS Fifteen (69%) eyes in the test group and 8 (36%) eyes in the control group achieved > or =20/25 uncorrected visual acuity 3 months after surgery, which was statistically significant (P<.05). The best spectacle-corrected visual acuity was > or =20/20 in 14 (63%) eyes in the test group and 10 (45%) eyes in the control group. The mean surgically induced astigmatism in the test group was 0.58+/-0.39 diopters (D) compared with 0.73+/-0.41 D in the control group. The change in corneal astigmatism from preoperative to 3 months after surgery was -0.17+/-0.32 D for the test group and 0.10+/-0.41 D for the control group, which was statistically significant (P<.05). The RMS value of trefoil aberrations increased, and all other aberrations decreased at 3 months after surgery in the test group. The RMS values of all corneal high order aberrations increased in the control group, with the increase in trefoil being statistically significant. The comparison of surgically induced high order aberrations between the two groups showed that corneal coma, trefoil, and secondary coma were significantly different. CONCLUSIONS Clear corneal tunnel phacoemulsification and IOL implantation guided by corneal topography can yield better visual acuity by reducing the pre-existing astigmatism and inducing less corneal aberrations than conventional temporal corneal tunnel phacoemulsification.

Efficient Generation of Lens Progenitor Cells from Cataract Patient–Specific Induced Pluripotent Stem Cells

The development of a technique to induce the transformation of somatic cells to a pluripotent state via the ectopic expression of defined transcription factors was a transformational event in the field of regenerative medicine. The development of this technique also impacted ophthalmology, as patient-specific induced pluripotent stemcells (iPSCs) may be useful resources for some ophthalmological diseases. The lens is a key refractive element in the eye that focuses images of the visual world onto the retina. To establish a new model for drug screening to treat lens diseases and investigating lens aging and development, we examined whether human lens epithelial cells (HLECs) could be induced into iPSCs and if lens-specific differentiation of these cells could be achieved under defined chemical conditions. We first efficiently reprogrammed HLECs from age-related cataract patients to iPSCs with OCT-4, SOX-2, and KLF-4. The resulting HLEC-derived iPS (HLE-iPS) colonies were indistinguishable from human ES cells with respect to morphology, gene expression, pluripotent marker expression and their ability to generate all embryonic germ-cell layers. Next, we performed a 3-step induction procedure: HLE-iPS cells were differentiated into large numbers of lens progenitor-like cells with defined factors (Noggin, BMP and FGF2), and we determined that these cells expressed lens-specific markers (PAX6, SOX2, SIX3, CRYAB, CRYAA, BFSP1, and MIP). In addition, HLE-iPS-derived lens cells exhibited reduced expression of epithelial mesenchymal transition (EMT) markers compared with human embryonic stem cells (hESCs) and fibroblast-derived iPSCs. Our study describes a highly efficient procedure for generating lens progenitor cells from cataract patient HLEC-derived iPSCs. These patient-derived pluripotent cells provide a valuable model for studying the developmental and molecular biological mechanisms that underlie cell determination in lens development and cataract pathophysiology.

The polyamidoamine-mediated inhibition of bcl-2 by small hairpin RNA to induce apoptosis in human lens epithelial cells

The Brønsted-acidic ionic liquid 1-methyl-3-(4-sulfobutyl)imidazolium triflate [BMIM(SO3H)][OTf] was demonstrated to act efficiently as solvent and catalyst for the halogenation of activated organic compounds with N-halosuccinimides (NXS) under mild conditions with short reaction times. Methyl aryl ketones were converted into α-halo and α,α-dihaloketones, depending on the quantity of NXS used. Ketones with activated aromatic rings were selectively halogenated, however in some cases mixtures of α-halogenated ketone and ring-halogenated ketones were obtained. Activated aromatics were regioselectively ring halogenated to give mono- and dihalo-substituted products. The [BMIM(SO3H)][OTf] ionic liquid (IL-A) was successfully reused eight times in a representative monohalogenation reaction with no noticeable decrease in efficiency. An effective halogenation scale-up in this IL is also presented. The reactivity trend and the observed chemo- and regioselectiivities point to an ET process in these IL-promoted halofunctionalization reactions.

Noninvasive Keratograph assessment of tear film break-up time and location in patients with age-related cataracts and dry eye syndrome:

Objective To investigate tear-film break-up time and spatial distribution via noninvasive Keratograph 4 in patients with cataracts and dry eye syndrome (DES). Methods Noninvasive first break-up time (NIKf-BUT) and average break-up time (NIKav-BUT) were evaluated via Keratograph 4 in patients with age-related cataracts and DES. The location and size of tear break regions were recorded and the distribution of first break-up areas was summarized. Patients also underwent conventional break-up time assessments (TBUT test and Schirmer’s test). Results A total of 43 left and 43 right eyes were examined. There was no significant difference between TBUT and NIKav-BUT. NIKf-BUT was significantly shorter than TBUT. Both NIKf-BUT and NIKav-BUT correlated positively with TBUT. In both the left and right eye, the most common first break-up areas were the peripheral domain of the inferior precorneal surface and the central domain of the superior portion. Conclusions The Keratograph 4 appears to provide an effective noninvasive method for assessing tear film, enabling effective preoperative evaluation of tear film break-up regularity, informing the location of the incision and reducing the probability of postoperative DES.

Liquid-chromatographic and mass-spectrometric identification of lens proteins using microwave-assisted digestion with trypsin-immobilized magnetic nanoparticles

We used a newly developed method combining trypsin-immobilized magnetic nanoparticles (TIMNs) and microwave-assisted protein digestion to study the proteins of human lens tissue. The digested proteins were identified by liquid chromatography and mass spectrometry. The lens proteins were digested under optimized conditions (digestion time 1 min, microwave power 400 W, trypsin-to-protein ratio 1:5) determined using bovine serum albumin as the standard protein, before liquid-chromatographic and mass-spectrometric analysis. Twenty-six proteins were identified with the new digestion method compared with 11 proteins identified with traditional in-solution digestion (12h). gamma-Crystallin, beta-crystallin, and superoxide dismutase 1 proteins, identified with the microwave-assisted method but not the traditional method, are related to cataract development according to some studies. The TIMNs were easily separated from the digestion products. This new digestion method could prove extremely useful for large-scale proteomic analyses.

LOXL1 Hypermethylation in Pseudoexfoliation Syndrome in the Uighur Population

PURPOSE High prevalence of pseudoexfoliation syndrome (PEX) occurs in the Uighur population. This study investigated DNA methylation of the lysyloxidase-like 1 (LOXL1) gene in Uighur PEX patients with cataracts. METHODS The research involved 10 lens capsule specimens from Uighur PEX patients with cataracts and 10 lens capsule specimens from Uighur control patients with age-related cataract (ARC) alone. All specimens were freshly collected during cataract surgery. Methylation status of the CpG islands was analyzed using pyrosequencing. The mRNA levels of LOXL1 were evaluated by quantitative real-time PCR, and protein levels were evaluated by Western blot assay. RESULTS For all the six chosen CpG islands of the LOXL1 gene promoter, hypermethylation was found in the PEX with cataracts compared to the age-matched ARC group. At the same time, the expression level of LOXL1 mRNA was significantly reduced in the PEX with cataracts group than that in the ARC group, and the expression level of the LOXL1 protein product demonstrated a similar tendency. CONCLUSIONS The susceptible PEX gene LOXL1 undergoes DNA hypermethylation in its promoter region in Uighur PEX with cataracts patients. This indicates that epigenetic regulation might play roles in PEX pathogenesis.

αA Crystallin May Protect against Geographic Atrophy—Meta-Analysis of Cataract vs. Cataract Surgery for Geographic Atrophy and Experimental Studies

Background Cataract and geographic atrophy (GA, also called advanced “dry” age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies. Methods/Principal Findings We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84–7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR = 3.23, 95% CI: 0.63–16.47). Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO3 in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice. Conclusions Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.

Long-Term Visual Outcomes of Secondary Intraocular Lens Implantation in Children with Congenital Cataracts

Aim The aim of this study was to evaluate the long-term visual outcomes and factors affecting visual results in children undergoing secondary intraocular lens (IOL) implantation following primary congenital cataract extraction. Methods Children with congenital cataracts who underwent secondary IOL implantation for aphakia at the Eye and ENT Hospital of Fudan University between January 1, 2001, and December 31, 2007, were retrospectively reviewed. One eye was randomly selected in children with bilateral cataracts. Laterality, type of cataract (total or partial opacity), sex, age at primary and secondary surgeries, visual axis opacity (VAO), compliance with amblyopia therapy, postoperative ocular complications, refractive error, ocular alignment, and best corrected visual acuity (BCVA) at last follow-up were recorded; potential factors that might have affected the visual results were evaluated. Results Seventy-six bilateral and 34 unilateral congenital cataract cases were analyzed; the mean ages of the children were 12.70±5.06 and 12.50±2.71 years at final follow-up, the mean follow-up periods from IOL implantation were 94.93±24.22 and 109.09±18.89 months, and the mean BCVA (Log MAR) values were 0.51±0.37 and 1.05±0.46, respectively. Final BCVA after secondary IOL implantation was significantly associated with laterality, type of cataract, age at primary cataract extraction, compliance with amblyopia therapy, and refractive correction after surgery. No significant associations were found between BCVA and sex, age at secondary IOL implantation, VAO, or other ocular complications. The most common ocular complications were VAO and elevated intraocular pressure after surgery. There were no other complications, with the exception of one eye with IOL dislocation. Conclusions The results indicate that the important determinants of long-term visual outcomes in children with congenital cataracts undergoing secondary IOL implantation are laterality, cataract type, age at initial cataract extraction, compliance with amblyopia therapy, and refractive error.

Effects of histone acetylation on superoxide dismutase 1 gene expression in the pathogenesis of senile cataract

Histone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types—nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)—using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly. Both H3 and H4 were deacetylated at −600 bp of the SOD1 promoter of cataract lenses, and hypoacetylated at −1500, −1200, and −900 bp. In hypoacetylated histones, the hypoacetylation pattern differed among the cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4 acetylation at the SOD1 promoter, decreased protein expression, and induced cataract formation in rabbits. AA also inhibited HLEC viability and increased cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop AA’s effects on both rabbit lenses and HLECs. Decreased histone acetylation at the SOD1 promoter is associated with declined SOD1 expression in senile cataracts. Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts.

The efficacy of lens removal plus IOL implantation for the treatment of spherophakia with secondary glaucoma

Aims To evaluate the efficacy of lens removal plus intraocular lens (IOL) implantation for spherophakia with secondary glaucoma. Methods A series of 19 patients (n=24 eyes) were split into two groups according to the degree of zonular abnormality as follows: group 1 (within the range of one quadrant, n=7 eyes) and group 2 (beyond the range of one quadrant, n=17 eyes). The patients in group 1 underwent phacoemulsification+capsular tension ring (CTR)+IOL, whereas patients in group 2 underwent pars plana lensectomy with scleral-fixated posterior chamber (PC) IOL implantation. The best corrected visual acuity (BCVA) (logMAR unit) and intraocular pressure (IOP) were documented at presentation and at 1 day, 7 days, 3 months, 1 year and 3 years postoperatively. Results The IOP in both groups significantly decreased after surgery (group 1:28.84±5.36 mm Hg at presentation, 15.86±0.79 mm Hg at the 3-year visit, t=6.34, p=0.000; group 2:26.18±12.16 mm Hg at presentation, 14.54±3.40 mm Hg at the 3-year visit, t=3.80, p=0.01). The BCVA increased from 0.79±0.36 at baseline to 0.44±0.38 at the 3-year follow-up but did not reach a significantly different level in group 1 (t=1.72, p=0.11), whereas the BCVA significantly increased from 1.15±0.75 at baseline to 0.43±0.38 at the 3-year visit in group 2 (t=3.45, p=0.02). Conclusions Both phacoemulsification+CTR+IOL and lensectomy with scleral-fixated PC IOL implantation are effective in lowering the IOP and enhancing the visual acuity in patients with spherophakia and secondary glaucoma.