Mir-204-5p alleviates mitochondrial dysfunction by targeting IGFBP5 in diabetic cataract.

BACKGROUND: Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive. METHODS AND RESULT: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model. CONCLUSIONS: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.

Late postoperative opacification of a new type hydrophilic acrylic intraocular lens.

Background: To report the clinical consequences and laboratory characteristics of late postoperative opacification of a hydrophilic acrylic intraocular lens (US-860UV IOL) as well as the prognosis of IOL replacement. Methods: Forty medical records (42 eyes) of patients with US-860UV IOL opacification reporting decreased or lost vision who underwent IOL explantation between 2017 and 2019 were reviewed. Explanted IOLs were analyzed by slit-lamp examination, confocal microscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) at the Shandong Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, and Qingdao University of Science and Technology, Qingdao, China. Results: The mean age of the 40 patients was 74.83 â€‹± â€‹7.57 (63-92) years. The mean interval between cataract surgery and diagnosis of opacification was 32.38 â€‹± â€‹8.76 (17-48) months. Systemic diseases were found without statistical correlations, the most frequent being arterial hypertension, coronary heart disease, and diabetes mellitus. Visual acuity improved from 1.42 â€‹± â€‹1.03 to 0.31 â€‹± â€‹0.16 (logMAR) after IOL replacement. SEM, EDS and alizarin red staining showed uniformly distributed, diffuse, milk-white opacification, with calcium and phosphorus deposits on the optic and haptic surfaces that could be dissolved in 1% HCl. Conclusions: Calcium and phosphorus deposition was the main cause of hydrophilic acrylic US-860UV IOL opacification. IOL replacement can safely and effectively improve the visual acuity of patients.

Incidence and Risk Factors of Repositioning Surgery to Correct Misalignment of Toric Intraocular Lenses After Cataract Surgery：A Single-Center Retrospective Observational Study.

PURPOSE: To analyze the incidence and outcomes of repositioning surgery to correct misalignment of several toric intraocular lenses (IOLs) after cataract surgery. METHODS: In this retrospective study, patients who underwent repositioning surgery to correct misalignment of toric IOLs following cataract surgery between January 2019 and December 2021 were enrolled. The medical data on patients' age, gender, preoperative axial length, corneal astigmatism, the axis of astigmatism, IOL models, IOL axis, uncorrected distance visual acuity, residual refraction, and postoperative outcomes were analyzed. RESULTS: Among the 1135 eyes implanted with toric IOLs at Qingdao Eye Hospital, 23 (2.026%, 23/1135) underwent repositioning surgery. Univariate analysis revealed that the incidence of repositioning surgery was significantly lower with AcrySof (0.636%, 5/786) than with ZEISS (2.959%, 5/169) and TECNIS (7.222%, 13/180) IOL platforms; The incidence of repositioning surgery with monofocal toric IOLs (1.169%, 11/941) was significantly lower than multifocal toric IOLs (6.186%, 12/194) (P<0.001); Additionally, a significant difference in age was also observed (P=0.002). Multivariate logistic regression analysis showed that IOL platform (P=0.004) and younger age (P=0.006) were independent risk factors for repositioning surgery. CONCLUSION: The incidence of repositioning surgery of toric IOLs after cataract surgery was 2.026%. It was linked to the IOL platform, multifocal toric IOLs, and younger age.

Comparison Between L-312 Hydrophobic-Hydrophilic Acrylate and US-860 UV Hydrophilic Acrylate IOL Opacification Characteristic.

Objective: To compare opacity characteristics of US-860 UV and L-312 IOL, and report the phenomenon of glistenings in hydrophobic-hydrophilic acrylic IOLs. Setting: Qingdao Eye Hospital. Design: Experimental study. Methods: Four medical records (4 eyes) of patients with L-312 or US-860 UV IOL opacification reporting decreased or lost vision who underwent IOL explanation between 2019 and 2021 were reviewed. Explanted IOLs were analyzed by slit-lamp examination, confocal microscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) at Qingdao Eye Hospital and Qingdao university of science and technology. Results: The 4 explanted IOLs were represented by 2 hydrophilic acrylic designs. The preoperative mean corrected distance visual acuity changed from 1.84 ± 1.09 logarithm of the minimum angle of resolution (log MAR) to 0.20 ± 0.03 log MAR postoperatively except case 3. The mean interval of the L-312 IOL was 56.67 ± 14.19 months (range 44 to 72 months), and the interval of the US-860 UV IOL was 27 months. Morphological findings were surface, subsurface calcifications of the US-860 UV IOL material, and the optical region of L-312 IOLs are teeming with a great number of vacuoles by light microscope, scanning electron microscope and Energy Dispersive X-ray Spectral. Conclusion: The cause of US-860 UV opacification was primary calcification, and vacuoles resulted in L-312 IOL opacification.

Intraoperative and Postoperative Intraocular Lens Opacifications: Analysis of 42545 Cases.

PURPOSE: To assess the types and causes of intraocular lens (IOL) turbidity in a tertiary eye center. Setting. Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China. DESIGN: Retrospective case series. METHODS: Patients who underwent uncomplicated phacoemulsification and IOL implantation for cataract between January 2015 and December 2019 were included. Medical records were reviewed of participants with intraoperative or postoperative IOL opacification for clinical data, artificial crystal materials, and causes of the opacification. RESULTS: A total of 42545 IOLs were implanted in the five years, comprising 25471 (66.0%) hydrophilic IOLs, 11881 (27.9%) hydrophobic IOLs, and 2601 (6.1%) hydrophilic-hydrophobic acrylic IOLs. Among the operated eyes, 14 eyes (13 patients) experienced IOL opacification, which was permanent for 10 IOLs, including 7 (0.6%) hydrophilic IOLs (860UV) and 3 (0.2%) hydrophilic-hydrophobic acrylic IOLs (L-312). The mean interval between surgery and diagnosis of permanent opacification was 34.4 ± 18.4 (SD) months (range, 12 to 59 months). Permanent IOL clouding led to a statistically significant reduction in best corrected visual acuity (mean, 0.64 ± 0.4 logMAR; P < 0.004). Acute IOL clouding occurred in four eyes during the implantation of a hydrophilic-hydrophobic acrylic IOL of L-312, 809M, or 839M and returned to transparency several hours later. All four procedures were performed in winter, with the mean outside temperature being -5.75°C. CONCLUSIONS: The rate of IOL opacification was 0.03%. Both delayed postoperative and acute intraoperative opacifications occurred with various characteristics in IOLs made of different materials and designs. Clinicians should be aware of this risk for cataract surgery.

Clinical Features, Risk Factors, and Therapy of Epithelial Keratitis after Cataract Surgery.

PURPOSE: The study aimed to assess the clinical characteristics, risk factors, and therapy of epithelial keratitis after cataract surgery. METHODS: Medical data of 89 consecutive patients who developed epithelial keratitis after cataract surgery, including 37 patients with diabetes mellitus (37 eyes) and 52 patients without diabetes mellitus (52 eyes), were retrospectively reviewed. The clinical characteristics, risk factors, and therapy in those patients were evaluated. RESULTS: The preoperative tear film function determined by the tear breakup time, meibomian gland atrophy score, and low tear meniscus height in diabetic patients was poorer than nondiabetic patients (P < 0.001). Of diabetic patients, 83.78% (31/37) had been diagnosed with meibomian gland dysfunction before cataract surgery and treated with topical nonsteroidal anti-inflammatory drugs after cataract surgery for 44.69 ± 10.51 days, compared to 42.31% (22/52) of nondiabetic patients receiving the topical nonsteroidal anti-inflammatory treatment for 33.35 ± 5.16 days (both P < 0.001). Epithelial lesions progressed within three to four days following cataract surgery in 59.46% (22/37) of diabetic patients, versus 30.77% (16/52) of the nondiabetic patients (P=0.025). Patients with combined meibomian gland dysfunction and epithelial defects accounted for 48.65% (18/37) in the diabetic group and 25.00% (13/52) in the nondiabetic group (P < 0.001). In vivo confocal microscopy showed absence of subbasal never fibers in eyes with epithelial defects, and central corneal sensation was also significantly depressed in those eyes, but there was no significant difference between the two groups (P=0.227). Corneal ulceration and herpes simplex keratitis were found in 2.70% (1/37) and 5.41% (2/37) of diabetic patients, respectively. Amniotic membrane transplantation was required in 32.43% (12/37) of patients in the diabetic group, and the proportion was higher than 1.92% (1/52) in the nondiabetic group (P < 0.001). Average healing time of the corneal epithelium in the diabetic group was 40.62 ± 20.0 days, much longer than 21.74 ± 6.94 days in the nondiabetic group (P=0.002). CONCLUSION: Epithelial keratitis after cataract surgery in diabetic patients has the characteristics of rapid development, severe epithelial damage, and slow repair of the corneal epithelium. Amniotic membrane transplantation is a good choice for persistent epithelial defects associated with such epithelial keratitis. Attention should be paid to the tear film function and use of topical nonsteroidal anti-inflammatory drugs in patients undergoing cataract surgery.

Long noncoding RNA DLEU2 drives the malignant behaviors of thyroid cancer through mediating the miR-205-5p/TNFAIP8 axis.

OBJECTIVE: Considering the plight in thyroid cancer therapy, we aimed to find novel therapeutic targets from a molecular perspective. METHODS: Quantitative real-time PCR (qRT-PCR) and Western blot assay were carried out to determine RNA and protein expression. Cell counting kit-8 (CCK8) assay, flow cytometry, transwell migration assay and aerobic glycolysis analysis were performed to analyze cell proliferation, apoptosis, migration and aerobic glycolysis of thyroid cancer cells. MiRcode and Starbase software were used to search the downstream genes of long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 2 (DLEU2) and microRNA-205-5p (miR-205-5p), and the intermolecular combination was confirmed by dual-luciferase reporter assay. The in vivo role of DLEU2 in tumor growth was verified using the murine xenograft model. RESULTS: DLEU2 and tumor necrosis factor-α-induced protein 8 (TNFAIP8) were highly expressed in thyroid cancer tissues and cell lines. DLEU2 and TNRAIP8 promoted the proliferation, migration and aerobic glycolysis and restrained the apoptosis of thyroid cancer cells. DLEU2/miR-205-5p/TNFAIP8 signaling axis was identified in thyroid cancer cells. TNFAIP8 overexpression largely rescued the malignant phenotypes in DLEU2-silenced thyroid cancer cells. DLEU2 positively regulated TNFAIP8 expression by acting as miR-205-5p sponge in thyroid cancer cells. DLEU2 silencing blocked the growth of xenograft tumors in vivo. CONCLUSION: lncRNA DLEU2 exerted a pro-tumor role to promote proliferation, migration and aerobic glycolysis while repressing the apoptosis of thyroid cancer cells via miR-205-5p/TNFAIP8 axis.

AQP5 regulates vimentin expression via miR-124-3p.1 to protect lens transparency.

The pathogenesis of congenital cataract (CC), a major disease associated with blindness in infants, is complex and diverse. Aquaporin 5 (AQP5) represents an essential membrane water channel. In the present study, whole exome sequencing revealed a novel heterozygous missense mutation of AQP5 (c.152 T > C, p. L51P) in the four generations of the autosomal dominant CC (adCC) family. By constructing a mouse model of AQP5 knockout (KO) using the CRISPR/Cas9 technology, we observed that the lens of AQP5-KO mice showed mild opacity at approximately six months of age. miR-124-3p.1 expression was identified to be downregulated in the lens of AQP5-KO mice as evidenced by qRT-PCR analysis. A dual luciferase reporter assay confirmed that vimentin was a target gene of miR-124-3p.1. Organ-cultured AQP5-KO mouse lenses were showed increased opacity compared to those of WT mice, and vimentin expression was upregulated as determined by RT-PCR, western blotting, and immunofluorescence staining. After miR-124-3p.1 agomir was added, the lens opacity in WT mice and AQP5-KO mice decreased, accompanied by the downregulation of vimentin. AQP5-L51P increased vimentin expression of in human lens epithelial cells. Therefore, a missense mutation in AQP5 (c.152 T > C, p. L51P) was associated with adCC, and AQP5 could participate in the maintenance of lens transparency by regulating vimentin expression via miR-124-3p.1.

Proteomic analysis of aqueous humor from cataract patients with retinitis pigmentosa.

A postcataract surgery complication in patients with retinitis pigmentosa (RP) is lens capsular contraction. To identify potential proteins contributing to this phenomenon, high-performance liquid chromatography/mass spectrometry-based proteomic analysis was conducted with aqueous humor samples collected from 11 patients who underwent cataract surgeries, with four patients diagnosed as RP and cataract (RP group) and the other seven with only senile cataract group. The upregulated proteins in the RP group were enriched in wound response, while downregulated proteins were enriched in cell adhesion and lens crystallins. Receptors of two dramatically upregulated proteins tenascin-C (TNC) and serotransferrin were found expressed in human lens epithelial cells (HLEs). TNC can promote primary HLEs proliferation and cell line HLE-B3 migration. This study indicates aqueous humor proteomic analysis serves as an effective way to unveil the pathogenesis of RP complications. TNC is a potential target of stimulating HLEs proliferation in RP concomitant cataract patients that worth further research.

Cataract surgery contributes to ocular axis growth of aphakic eyes in infants with complex microphthalmos.

To observe the ocular axis, visual acuity and intraocular pressure (IOP) of aphakic eye in infants with congenital cataract and complex microphthalmos after first-stage cataract surgery.This retrospective study included infants with congenital cataract and operated at the Qingdao Eye Hospital between January 2010 and December 2014. The infants were divided into 2 groups: preoperative axial length <18 mm (microphthalmos) or ≥18 mm (controls). Follow-up lasted 24 months; visual acuity, axial length, and IOP were evaluated.There were 28 infants (55 eyes) in the microphthalmos group and 35 (61 eyes) in the control group. The preoperative visual acuity was negative for optokinetic nystagmus, while the postoperative visual acuity was positive for optokinetic nystagmus in both groups. The growth rate was higher in the microphthalmos group (1.4 ±â€Š0.8 vs 0.8 ±â€Š0.4 mm/yr, P < .001 vs controls). The axial length was smaller in the microphthalmos group at all time points compared with the control group (all P < .001). There was no changes in IOP in the microphthalmos group from baseline to 24 months (P = .147), but the IOP was slightly decreased in the control group (P = .015).Cataract surgery may contribute to ocular axis growth in infants with complex microphthalmos.

DNase I improves corneal epithelial and nerve regeneration in diabetic mice.

DNase I has been reported to improve diabetic wound healing through the clearance of neutrophils extracellular traps (NETs) caused by neutrophil aggregation. However, the function of DNase I on diabetic corneal wound healing remains unclear. Here, we investigated the effect and mechanism of topical DNase I application on diabetic mouse corneal epithelial and nerve regeneration. Corneal epithelial defects, inflammatory response, regeneration-related signalling pathways, oxidative stress, corneal innervation and sensation were examined and compared between the diabetic and normal mice. The results confirmed firstly the increased NETs production during the delayed corneal epithelial wound healing of diabetic mice, which was significantly improved through either DNase I or Cl-amidine administration. Mechanistically, DNase I improved inflammation resolution, reactivated epithelial regeneration-related signalling pathways and attenuated the accumulation of reactive oxygen species (ROS). Moreover, DNase I application also promoted corneal nerve regeneration and restored the impaired corneal sensitivity in diabetic mice. Therefore, these results indicate that topical DNase I application promotes corneal epithelial wound healing and mechanical sensation restoration in diabetic mice, representing the potential therapeutic approach for diabetic keratopathy.

A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has become an important public health issue in the world. More than 118 000 cases were confirmed around the world. The main clinical manifestations were respiratory symptoms and occasional gastrointestinal symptoms. However, there is no unified standard for the diagnosis and treatment of COVID-19. In the retrospective analysis, we report nine cases of COVID-19, describe the history of contact, clinical manifestations, the course of diagnosis and clinical treatment before, during and after treatment.

Functional characterization of a novel GUCA1A missense mutation (D144G) in autosomal dominant cone dystrophy: A novel pathogenic GUCA1A variant in COD.

Purpose: To elucidate the clinical phenotypes and pathogenesis of a novel missense mutation in guanylate cyclase activator A1A (GUCA1A) associated with autosomal dominant cone dystrophy (adCOD). Methods: The members of a family with adCOD were clinically evaluated. Relevant genes were captured before being sequenced with targeted next-generation sequencing and confirmed with Sanger sequencing. Sequence analysis was made of the conservativeness of mutant residues. An enzyme-linked immunosorbent assay (ELISA) was implemented to detect the cyclic guanosine monophosphate (cGMP) concentration. Then limited protein hydrolysis and an electrophoresis shift were used to assess possible changes in the structure. Coimmunoprecipitation was employed to analyze the interaction between GCAP1 and retGC1. Immunofluorescence staining was performed to observe the colocalization of GCAP1 and retGC1 in human embryonic kidney (HEK)-293 cells. Results: A pathogenic mutation in GUCA1A (c.431A>G, p.D144G, exon 5) was revealed in four generations of a family with adCOD. GUCA1A encodes guanylate cyclase activating protein 1 (GCAP1). D144, located in the EF4 loop involving calcium binding, was highly conserved in the species. GCAP1-D144G was more susceptible to hydrolysis, and the mobility of the D144G band became slower in the presence of Ca2+. At high Ca2+ concentrations, GCAP1-D144G stimulated retGC1 in the HEK-293 membrane to significantly increase intracellular cGMP protein concentrations. Compared with wild-type (WT) GCAP1, GCAP1-D144G had an increased interaction with retGC1, as detected in the coimmunoprecipitation assay. Conclusions: The newly discovered missense mutation in GUCA1A (p.D144G) might lead to an imbalance of Ca2+ and cGMP homeostasis and eventually, cause a significant variation in adCOD.

The Demography and Etiology of Pediatric Enucleation in a Tertiary Eye Center in North China, 2001-2015.

PURPOSE: To review the demography and etiology of pediatric enucleation over time. METHODS: Pediatric ophthalmic inpatients recruited and recorded (aged 0-14 years) at Shandong Eye Institute from January 2001 to December 2015 were reviewed. Changes during the three periods from 2001 to 2005, 2006 to 2010, and 2011 to 2015 were compared and analyzed. RESULTS: A total of 9307 pediatric inpatients were reviewed. Of these, 71 patients (71 eyes) who had been treated by enucleation were analyzed; 46 were boys (64.79%) and 25 were girls (35.21%). The mean age at enucleation was 9 (0-14) years. The pediatric enucleation rate during this 15-year period was 0.76% (71/9307), with a decreasing trend (p < 0.001). From 2001 to 2005, the figure was 3.45% (43/1245); it dropped to 0.80% (26/3231) from 2006 to 2010 and then dropped further to 0.04% (2/4831) by 2015. Trauma (52.1%, 37/71) was the leading etiology. Overall, 89.2% (33 eyes) exhibited open globe injuries; 78.4% (29/37) of these involved boys. In the cases with open injuries, the mean age at the time of trauma was 6.0 (0-14) years and the mean age at enucleation was 11 (2-14) years. Retinoblastoma (RB) (22.5%, 16/71) was the second-most common etiology; 68.8% (11/16) of these cases involved girls and the mean age at enucleation was 2 (0-5) years. CONCLUSION: A decrease in pediatric enucleation in North China, especially in Shandong Province, was observed over time, possibly because of better surgical techniques, improvements in the treatment of RB, and public health interventions in children.

Reference Intervals of Cytokeratin-19 Fragment (CYFRA 21-1) in Healthy Adults in China.

BACKGROUND: The reference intervals for serum cytokeratin-19 fragment (CYFRA 21-1) have not been established in Chinese population. This study aimed to measure serum CYFRA 21-1 levels in healthy Chinese subjects. METHODS: This cross-sectional, four-center study in two Chinese provinces enrolled participants (aged 18 - 85 years) with normal liver/kidney function and normal results for routine blood tests/urinalysis. Serum CYFRA 211 level was measured by ARCHITECT immunoassay (Abbott Diagnostics). RESULTS: The study included 3,366 participants. The median (interquartile range) value for serum CYFRA 21-1 level was 1.38 (1.00 - 1.89) ng/mL and tended to increase with age. The upper limit of the 97.5th percentile was 3.55 ng/mL and tended to increase with age. Serum CYFRA 21-1 median level varied between the four centers from 1.22 (0.89, 1.71) to 1.55 (1.12, 2.18) ng/mL, while the 97.5th percentile varied from 3.24 to 4.09 ng/mL. CYFRA 21-1 level correlated weakly with age and creatinine level. CONCLUSIONS: These new data can help to establish the 'normal range' of serum CYFRA 21-1 in people in China.

A Chinese family with Axenfeld-Rieger syndrome: report of the clinical and genetic findings.

AIM: To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome (ARS) and characterize the molecular defect in PITX2 in the family. METHODS: Patients presented with typical ARS from a Chinese family were investigated. We performed genome-wide linkage scan and exome sequencing to identify the pathogenic mutations. Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS: Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A>G substitution at position -11 of 3'ss of exon 5 (IVS5-11A>G) that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family. CONCLUSION: Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.

Visual performance with accommodating and multifocal intraocular lenses.

AIM: To compare the visual functional outcomes with accommodating and multifocal intraocular lenses (IOLs). METHODS: Our retrospective comparative study included 51 patients (60 eyes) received implantation of an accommodating IOL (Tetraflex; 16 patients, 20 eyes), a refractive multifocal IOL (ReZoom; 18 patients, 20 eyes), or a diffractive multifocal IOL (ZMA00; 17 patients, 20 eyes). Subjective refraction, visual acuity, contrast sensitivity (CS), intraocular aberration, and subjective photic phenomena were detected at 3mo after surgery. RESULTS: The spherical equivalent in the three groups was -0.38±0.54 D, 0.14±0.56 D, and 0.35±0.41 D, respectively. No statistically significant differences were found in uncorrected and corrected distance visual acuity and uncorrected intermediate visual acuity among the groups (P=0.39). The ReZoom group had significantly better distance-corrected intermediate visual acuity than the ZMA00 group (P=0.003). The ZMA00 group had significantly better near visual acuity than the other groups (P<0.05). Better contrast sensitivity values were observed in the Tetraflex group under most of the spatial frequencies conditions (P=0.025). The total aberration was lowest in the ZMA00 group (P=0.000), and the spherical aberration was highest in the Tetraflex group (P=0.000). The three groups had similar frequency of ghosting and glare, and the Tetraflex group had a low rate of halos (P=0.01). CONCLUSION: Both accommodating and multifocal IOLs can successfully restore distance and uncorrected intermediate visual acuities. Tetraflex accommodating IOLs perform better in CS and with less halos of photic phenomena. ReZoom refractive multifocal IOLs have better performance in distance-corrected intermediate visual acuity than ZMA00 diffractive multifocal IOLs, and the latter achieved better near visual acuity and efficiently decreased the optical aberration.

microRNA-182 Mediates Sirt1-Induced Diabetic Corneal Nerve Regeneration.

Sensory neurons are particularly susceptible to neuronal damage in diabetes, and silent mating type information regulation 2 homolog 1 (Sirt1) has been recently identified as a key gene in neuroprotection and wound healing. We found that the expression of Sirt1 was downregulated in trigeminal sensory neurons of diabetic mice. A microRNA microarray analysis identified microRNA-182 (miR-182) as a Sirt1 downstream effector, and the expression level of miR-182 was increased by Sirt1 overexpression in trigeminal neurons; Sirt1 bound to the promoter of miR-182 and regulated its transcription. We also revealed that miR-182 enhanced neurite outgrowth in isolated trigeminal sensory neurons and overcame the detrimental effects of hyperglycemia by stimulating corneal nerve regeneration by decreasing the expression of one of its target genes, NOX4. Furthermore, the effects of miR-182 on corneal nerve regeneration are associated with a functional recovery of corneal sensation in hyperglycemic conditions. These data demonstrate that miR-182 is a key regulator in diabetic corneal nerve regeneration through targeting NOX4, suggesting that miR-182 might be a potential target for the treatment of diabetic sensory nerve regeneration and diabetic keratopathy.

Neuropeptide FF Promotes Recovery of Corneal Nerve Injury Associated With Hyperglycemia.

PURPOSE: To investigate how the neuropeptide FF (NPFF) promotes the recovery of corneal nerve injury associated with hyperglycemia. METHODS: Gene expression was analyzed using neurotrophin and receptor RT2 profiler polymerase chain reaction arrays in trigeminal (TG) sensory neurons. The role of NPFF in the regeneration of diabetic TG nerves was investigated in vitro by using cultured TG neurons from diabetic BKS.Cg-m+/+Leprdb/J (db/db) mice and in vivo by following corneal injury healing responses. RF9, a selective NPFF receptor (NPFF2R) antagonist, was used to prevent the interactions between NPFF and NPFF2R. RESULTS: Using a mRNA real-time PCR array, NPFF was found to be significantly lower in diabetic TG sensory neurons. Hyperglycemia induced the deficiency of ocular properties in db/db mice. The application of NPFF enhanced neurite elongation in diabetic TG neurons. Through subconjunctival injection, NPFF promoted corneal nerve injury recovery and epithelial wound healing in db/db mice. Furthermore, the application of NPFF rescued the activation of SIRT1 and PPAR-gamma, and downregulated the expression of PTEN and Rb in diabetic TG neurons. The promotion of NPFF on diabetic corneal epithelial healing and corneal innervations was completely abolished by RF9. Moreover, subconjunctivally injected NPFF accelerated the reinnervation of corneal nerves via the ERK1/2 pathway. CONCLUSIONS: These results indicate that NPFF signaling through NPFFR2 contributes to diabetic corneal nerve injury recovery and epithelial wound healing. Neuropeptide FF is a potential neuroregenerative factor for diabetic sensory nerve injury. Chinese Abstract.

Mutations in the ABCA3 gene are associated with cataract-microcornea syndrome.

PURPOSE: Cataract-microcornea syndrome (CCMC) is an autosomal dominant inherited disease characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although mutations of several genes have been shown to cause dominant CCMC, in many patients the causative gene has not yet been identified. Our aim was to identify the disease-associated gene in Chinese patients with CCMC. METHODS: The CCMC patients from two unrelated Chinese families and 26 sporadic patients were enrolled. All the patients were screened by Sanger sequencing with no identified mutations. Genetic variations were screened by whole-exome sequencing and then validated using Sanger sequencing. RESULTS: By sequencing the whole exome of three patients in a Chinese four-generation dominant CCMC family (Family A), three heterozygous missense mutation (c.115C>G, c.277G>A, and c.4393G>A) were identified in ATP-binding cassette protein A3 (ABCA3). At highly conserved positions, changes (c.115C>G and c.4393G>A) were predicted to have functional impacts and completely cosegregated with the phenotype. We further confirmed our finding by identifying another heterozygous missense mutation, c.2408C>T, in ABCA3 in an additional dominant CCMC family (Family B), which also cosegregated with the phenotype. Moreover, four heterozygous mutations, two missense mutations (c.4253A>T, c.2069A>T) and two splice site mutations (c.4053+2T>C, c.2765-1G>T) were identified from the sporadic patients. The ABCA3 protein was expressed in human lens capsule, choroid-retinal pigment epithelium and retinal pigment epithelial cells. CONCLUSIONS: Mutations in the human ABCA3 gene were associated with lethal respiratory distress. Our study showed, for the first time to our knowledge, that mutations in ABCA3 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder.