Decrease of lysyl hydroxylase 2 activity causes abnormal collagen molecular phenotypes, defective mineralization and compromised mechanical properties of bone.

Lysyl hydroxylase 2 (LH2) is an enzyme that catalyzes the hydroxylation of lysine (Lys) residues in fibrillar collagen telopeptides, a critical post-translational modification for the stability of intermolecular cross-links. Though abnormal LH2 activities have been implicated in various diseases including Bruck syndrome, the molecular basis of the pathologies is still not well understood. Since LH2 null mice die at early embryonic stage, we generated LH2 heterozygous (LH2+/-) mice in which LH2 level is significantly diminished, and characterized collagen and bone phenotypes using femurs. Compared to the wild-type (WT), LH2+/- collagen showed a significant decrease in the ratio of hydroxylysine (Hyl)- to the Lys-aldehyde-derived collagen cross-links without affecting the total number of aldehydes involved in cross-links. Mass spectrometric analysis revealed that, in LH2+/- type I collagen, the extent of hydroxylation of all telopeptidyl Lys residues was significantly decreased. In the helical domain, Lys hydroxylation at the cross-linking sites was either unaffected or slightly lower, but other sites were significantly diminished compared to WT. In LH2+/- femurs, mineral densities of cortical and cancellous bones were significantly decreased and the mechanical properties of cortical bones evaluated by nanoindentation analysis were compromised. When cultured, LH2+/- osteoblasts poorly produced mineralized nodules compared to WT osteoblasts. These data provide insight into the functionality of LH2 in collagen molecular phenotype and its critical role in bone matrix mineralization and mechanical properties.

Tspan15 plays a crucial role in metastasis in oral squamous cell carcinoma.

Tetraspanin 15 (Tspan15) is a member of the tetraspanin family, which is associated with various biological events and several diseases, however, its role in human oral squamous cell carcinoma (OSCC) remains unknown. The current study aimed to clarify the role of Tspan15 in OSCC. The mRNA and protein expression levels of Tspan15 were up-regulated in OSCC cases and OSCC-derived cell lines. Significant up-regulated Tspan15 expression was found in the advanced OSCC cases; primary tumoral size (P = 0.042), regional lymph node metastasis (P = 0.036) and TNM classification (P = 0.024). The decreased expression of Tspan15 did not significantly affect cellular proliferation, whereas tumoral invasion and migration activities were suppressed in Tspan15-down-regulated cells, suggesting that Tspan15 might activate metastasis-related signaling. Moreover, in the Tspan15-down-regulated cells, the expression of a disintegrin and metalloproteinase (ADAM) 10 was also down-regulated and the cells secreted less soluble N-cadherin compared with control cells. And weak immunoreactivity of ß-catenin in the nucleus was detected in Tspan15-down-regulated cells compared with the control cells. These findings suggested that overexpression of Tspan15 positively regulates development of OSCC, and that ADAM10, N-cadherin, ß-catenin might be involved in the Tspan15-mediated pathway. These unusual conditions of cell adhesion molecules may lead to high metastasis rate found in Tspan15-overexpressing cases.

Resveratrol Targets Urokinase-Type Plasminogen Activator Receptor Expression to Overcome Cetuximab-Resistance in Oral Squamous Cell Carcinoma.

Drug resistance to anti-cancer agents is a major concern regarding the successful treatment of malignant tumors. Recent studies have suggested that acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies such as cetuximab are in part caused by genetic alterations in patients with oral squamous cell carcinoma (OSCC). However, the molecular mechanisms employed by other complementary pathways that govern resistance remain unclear. In the current study, we performed gene expression profiling combined with extensive molecular validation to explore alternative mechanisms driving cetuximab-resistance in OSCC cells. Among the genes identified, we discovered that a urokinase-type plasminogen activator receptor (uPAR)/integrin ß1/Src/FAK signal circuit converges to regulate ERK1/2 phosphorylation and this pathway drives cetuximab-resistance in the absence of EGFR overexpression or acquired EGFR activating mutations. Notably, the polyphenolic phytoalexin resveratrol, inhibited uPAR expression and consequently the signaling molecules ERK1/2 downstream of EGFR thus revealing additive effects on promoting OSCC cetuximab-sensitivity in vitro and in vivo. The current findings indicate that uPAR expression plays a critical role in acquired cetuximab resistance of OSCC and that combination therapy with resveratrol may provide an attractive means for treating these patients.

UNC93B1 promotes tumoral growth by controlling the secretion level of granulocyte macrophage colony-stimulating factor in human oral cancer.

Unc-93 homolog B1 (UNC93B1), a transmembrane protein, is correlated with immune diseases, such as influenza, herpes simplex encephalitis, and the pathogenesis of systemic lupus erythematosus; however, the role of UNC93B1 in cancers including human oral squamous cell carcinomas (OSCCs) remains unknown. In the current study, we investigated the UNC93B1expression level in OSCCs using quantitative reverse transcription-polymerase chain reaction, immunoblot analysis, and immunohistochemistry. Our data showed that UNC93B1 mRNA and protein expressions increased markedly (p < 0.05) in OSCCs compared with normal cells and tissues and that high expression of UNC93B1 in OSCCs was related closely to tumoral size. UNC93B1 knockdown (shUNC93B1) OSCC cells showed decreased cellular proliferation by cell-cycle arrest in the G1 phase with up-regulation of p21Cip1 and down-regulation of CDK4, CDK6, cyclin D1, and cyclin E. We also found that granulocyte macrophage colony-stimulating factor (GM-CSF) was down-regulated significantly (p < 0.05) in shUNC93B1 OSCC cells. Moreover, inactivation of GM-CSF using neutralization antibody led to cell-cycle arrest at the G1 phase similar to the phenotype of the shUNC93B1 cells. The current findings indicated that UNC93B1 might play a crucial role in OSCC by controlling the secretion level of GM-CSF involved in tumoral growth and could be a potential therapeutic target for OSCCs.

Deficiency of lysyl hydroxylase 2 in mice causes systemic endoplasmic reticulum stress leading to early embryonic lethality.

Lysyl hydroxylase 2 (LH2) is an endoplasmic reticulum (ER)-resident enzyme that catalyzes the hydroxylation of lysine residues in the telopeptides of fibrillar collagens. This is a critical modification to determine the fate of collagen cross-linking pathway that contributes to the stability of collagen fibrils. Studies have demonstrated that the aberrant LH2 function causes various diseases including osteogenesis imperfecta, fibrosis, and cancer metastasis. However, surprisingly, a LH2-deficient animal model has not been reported. In the current study, to better understand the function of LH2, we generated LH2 gene knockout mice by CRISPR/Cas9 technology. LH2 deficiency was confirmed by genotyping polymerase chain reaction (PCR), reverse transcriptase-PCR, and immunohistochemical analyses. Homozygous LH2 knockout (LH2-/-) embryos failed to develop normally and died at early embryonic stage E10.5 with abnormal common ventricle in a heart, i.e., an insufficient wall, a thin ventricular wall, and loosely packed cells. In the LH2-/- mice, the ER stress-responsive genes, ATF4 and CHOP were significantly up-regulated leading to increased levels of Bax and cleaved caspase-3. These data indicate that LH2 plays an essential role in cardiac development through an ER stress-mediated apoptosis pathway.

Increased expression of tripartite motif (TRIM) like 2 promotes tumoral growth in human oral cancer.

Tripartite motif family-like 2 (TRIML2), a member of the TRIM proteins family, is closely related to Alzheimer's disease, however, no studies of TRIML2 have been published in the cancer research literature. In the current study, we investigated the expression level of TRIML2 and its molecular mechanisms in human oral squamous cell carcinoma (OSCC); reverse transcriptase-quantitative polymerase chain reaction, immunoblot analysis, and immunohistochemistry showed that TRIML2 is up-regulated significantly in OSCCs in vitro and in vivo. TRIML2 knockdown OSCC cells showed decreased cellular proliferation by cell-cycle arrest at G1 phase that resulted from down-regulation of CDK4, CDK6, and cyclin D1 and up-regulation of p21Cip1 and p27Kip1. Surprisingly, resveratrol, a polyphenol, led to not only down-regulation of TRIML2 but also cell-cycle arrest at G1 phase similar to TRIML2 knockdown experiments. Taken together, we concluded that TRIML2 might play a significant role in tumoral growth and that resveratrol may be a new drug for treating OSCC by interfering with TRIML2 function.

Neuron type-selective effects of activin on development of the hippocampus.

Activin is a member of the transforming growth factor-beta superfamily and affects the viability of hippocampal neurons during postnatal neurogenesis. We used primary hippocampal neuron to study the actions of activin on developing neurons. Continuous treatment of hippocampal cultures with activin suppressed the emergence of GAD67(+) neurons, which are a subtype of GABAergic interneurons, and increased the percentage of Prox1(+) neurons, which are dentate granule cells. The effects of activin were abolished by co-treatment with follistatin, which is a direct inhibitor of activin. In contrast, follistatin treatment alone increased the percentage of GAD67(+) neurons and decreased the percentage of Prox1(+) neurons. These results indicate that changes in activin signaling during postnatal neural development alter the composition of the neural circuitry and suggest that alterations in the ratio of excitatory to inhibitory neurons may be responsible for changes in the spontaneous and evoked-reactivity of these neurons to other neural inputs.

Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation.

BACKGROUND: The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (VASP/Ena-related gene upregulated during seizure and LTP, also known as homer-1a) is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S) is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L). Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5), the IP3 receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice. RESULTS: In this study, we generated short-form-specific gene targeting (KO) mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice. CONCLUSION: These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation.

Decreased postnatal neurogenesis in the hippocampus combined with stress experience during adolescence is accompanied by an enhanced incidence of behavioral pathologies in adult mice.

BACKGROUND: Adolescence is a vulnerable period in that stress experienced during this time can affect the incidence of psychiatric disorders later, during adulthood. Neurogenesis is known to be involved in the postnatal development of the brain, but its role in determining an individual's biological vulnerability to the onset of psychiatric disorders has not been addressed. RESULTS: We examined the role of postnatal neurogenesis during adolescence, a period between 3 to 8 weeks of age in rodents. Mice were X-irradiated at 4 weeks of age, to inhibit postnatal neurogenesis in the sub-granule cell layer of the hippocampus. Electrical footshock stress (FSS) was administered at 8 weeks old, the time at which neurons being recruited to granule cell layer were those that had begun their differentiation at 4 weeks of age, during X-irradiation. X-irradiated mice subjected to FSS during adolescence exhibited decreased locomotor activity in the novel open field, and showed prepulse inhibition deficits in adulthood. X-irradiation or FSS alone exerted no effects on these behaviors. CONCLUSION: These results suggest that mice with decreased postnatal neurogenesis during adolescence exhibit vulnerability to stress, and that persistence of this condition may result in decreased activity, and cognitive deficits in adulthood.

Alternative poly(A) site-selection regulates the production of alternatively spliced vesl-1/homer1 isoforms that encode postsynaptic scaffolding proteins.

The vesl-1/homer1 gene encodes a scaffold protein that interacts with several receptors to modulate synaptic functions. The gene also encodes two shorter forms that counteract the functions of the long form of Vesl. Expression of the shorter forms is driven by neural activities such as long-term potentiation. Here we analyzed the mechanism regulating vesl-1 alternative splicing. Each functional poly(A) site was in a different part of the 3'-terminal exon, with promoter-proximal and promoter-distal sites at the end of exons corresponding to the short and long form Vesl-1, respectively. 3'-End-processing at proximal poly(A) site, specifically at the vesl-1M poly(A) site, was enhanced by extracellular stimuli, thereby switching transcription termination from promoter-distal to -proximal poly(A) site. This switch was not specifically coupled to the vesl-1 promoter and was independent of de novo protein synthesis. Analysis of transcripts from mini-genes that mimic the structure of endogenous vesl-1 revealed that the vesl-1M poly(A) region plays a crucial role in switching to the alternative pre-mRNA splicing that is triggered by extracellular stimuli. Therefore, a 3'-end-processing event regulates the neural activity-dependent alternative splicing of vesl-1. This is the first report of a gene in which alternative poly(A) site-selection regulates alternative splicing in a protein synthesis-independent manner.

Functional role of prostacyclin receptor in rat dorsal root ganglion neurons.

Recent studies on prostanoids showed that some of prostanoid receptors are expressed in rat dorsal root ganglion (DRG) neurons. These facts suggest that prostanoid receptors might be involved in the excitation mechanism of DRG neurons. In the present study, PCR experiments revealed that one of prostanoid receptor, prostacyclin receptor (IP receptor) was expressed in L6 and S1 rat DRG neurons and that the expression of IP receptor was not changed in DRG neurons obtained from the cyclophosphamide (CYP)-induced cystitis rat. We examined the functional role of IP receptor agonist and other prostanoids by measuring cyclic AMP (cAMP) accumulation and substance P (SP) release in primary cultured DRG neurons. The pretreatment of DRG neurons with prostanoid agonists such as iloprost (IP), butaprost (EP(2)), misoprostol (EP(2-4)), PGE(2) (EP(1-4)) or PGD(2) (DP and CRTH2) sensitized the DRG neurons and hence potentiated the lys-bradykinin-induced SP release. The increase of SP release by lys-BK plus prostanoid agonists was proportion to cAMP accumulation. Iloprost was the most potent agonist to induce cAMP accumulation and SP release among prostanoid agonists evaluated in this study and its effect is mediated by IP receptor. Moreover, capsaicin-, ATP- and KCl-induced SP release was also enhanced by iloprost although iloprost did not change intracellular Ca(2+) and membrane depolarization induced by these chemical stimuli. These results strongly indicate that IP receptor play an important role in the sensitization of rat sensory neuron.

Cold response of the bladder in guinea pig: involvement of transient receptor potential channel, TRPM8.

OBJECTIVES: To address the physiologic role of TRPM8, one of the transient receptor potential channels, we investigated the bladder cooling reflex and the effect of menthol on it in the guinea pig. METHODS: Single cystometry in female Hartley guinea pigs was performed with high-speed infusion (60 mL/hr) under urethane anesthesia (1 g/kg intraperitoneally). The volume threshold for micturition (VT) and micturition pressure were determined. The distribution of TRPM8 in the S1 dorsal root ganglion (DRG) was also examined by immunostaining. RESULTS: Intravesical infusion of saline containing menthol (0.6 mM) at 38 degrees C markedly decreased the VT and increased micturition pressure. Although cold saline itself (4 degrees C) had little effect on VT or micturition pressure, the VT was significantly decreased in a temperature-dependent manner when the bladder was pretreated with menthol. This decrease in the VT was not observed in animals that received hexamethonium pretreatment (10 mg/kg intravenously), which blocks the spinal reflex, or capsaicin (1 mM intravesically), which causes deafferentation of capsaicin-sensitive C-fiber afferent. Immunohistochemical analysis revealed that TRPM8 is expressed in small-diameter neurons in guinea pig S1 dorsal root ganglions. CONCLUSIONS: The results of our study showed that the bladder cooling reflex is observed in guinea pigs if the animals were pretreated with menthol. This reflex was sensitive to ganglion blockade or capsaicin-sensitive C-fiber deafferentation and might be mediated by C-fiber activation through TRPM8.

Intraocular pressure rise after phacoemulsification surgery in glaucoma patients.

PURPOSE: To examine the changes in intraocular pressure (IOP) and the incidence of substantial rises in IOP in the early period after cataract surgery in eyes with open-angle glaucoma (OAG). SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: The study included 32 eyes of 32 patients with OAG and 31 control eyes of 31 age-matched patients scheduled for phacoemulsification surgery. The IOP was measured preoperatively and 1, 2, 3, 5, 7, 14, and 28 days postoperatively. The incidence of a substantial rise in IOP postoperatively was evaluated, with the criterion being an IOP higher than 30 mm Hg. RESULTS: In the OAG group, the mean IOP increased 1, 2, and 3 days postsurgery and then decreased, whereas in the control group, it decreased from day 1 postsurgery. Although no significant differences were found between groups preoperatively, the mean IOP in the OAG group was significantly higher than in the control group postoperatively. Furthermore, the mean IOP decrease was also less in the OAG group than in the control group. A substantial increase in IOP occurred at day 1 postsurgery in 4 eyes (12.5%) in the OAG group, whereas no eyes in the control group showed such an increase; this difference was significant (P =.0419). CONCLUSIONS: A substantial increase in IOP occurred in an approximately 13% of eyes with OAG 1 day after phacoemulsification surgery. The IOP shortly after surgery was significantly greater in the eyes with OAG than in nonglaucomatous eyes.

Correlation between posterior capsule opacification and visual function before and after Neodymium: YAG laser posterior capsulotomy.

PURPOSE: To investigate the correlation between visual acuity, contrast sensitivity, and contrast sensitivity with glare source (glare sensitivity), and the degree of posterior capsule opacification (PCO) before and after neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy. DESIGN: Prospective interventional case series. METHODS: Eighty-four patients (90 pseudophakic eyes) scheduled to undergo Nd:YAG laser capsulotomy were recruited. Visual acuity and contrast sensitivity with and without the presence of a circular glare source (using the contrast glare tester) were measured before and after Nd:YAG laser capsulotomy. The PCO density value was measured using a Scheimpflug videophotography system. The visual functions were statistically correlated with the PCO value. RESULTS: Before Nd:YAG laser capsulotomy, strong correlation existed between the PCO value and visual acuity (r = 0.728). Contrast sensitivity and glare sensitivity were also weakly correlated with the PCO value, but the correlation coefficients were smaller than that of visual acuity. After Nd:YAG laser capsulotomy, mean visual acuity, contrast sensitivity, and glare sensitivity at all visual angles improved significantly (P <.0001). After capsulotomy, no significant correlation was found between visual acuity, contrast sensitivity, or glare sensitivity and the PCO value. CONCLUSIONS: Before Nd:YAG laser capsulotomy, visual functions correlated significantly with the degree of PCO. Specifically, visual acuity has a stronger association with PCO than does contrast sensitivity or glare sensitivity and therefore should be considered to reflect most accurately the degree of PCO. After capsulotomy, these visual functions improve markedly and no longer have a significant correlation with PCO.

Aging changes in apparent accommodation in eyes with a monofocal intraocular lens.

PURPOSE: To examine the aging changes in the amplitude of apparent accommodation in eyes with a monofocal intraocular lens (IOL). DESIGN: Prospective comparative observational study. METHODS: Two hundred eyes of 200 patients who were scheduled for phacoemulsification and monofocal IOL implantation were studied. Forty patients in each of five age groups-younger than 40 years of age or in their 50s, 60s, 70s, and 80s-were prospectively recruited. Using an accommodopolyrecorder, the amplitude of apparent accommodation of these patients was measured approximately 1 month after surgery. Visual acuities from far to near distances after best-corrected distance were examined using an all-distance vision tester, and the region of accommodation at which each patient achieved a visual acuity of 20/29 or 20/40 was determined and converted to the diopteric range. Contrast sensitivity was also examined using a vision contrast test system. RESULTS: The amount of apparent accommodation as measured with the accommodopolyrecorder was decreased significantly in proportion to patient age (P <.0001). Furthermore, significant negative correlation was found between the amount of apparent accommodation and actual age of each patient (r = -.491). The diopteric range of accommodation at which the patients achieved 20/29 or 20/40 also reduced in proportion to the age. Although no significant differences were found in the mean far visual acuities between age groups, the intermediate and near visual acuities worsened significantly with age. The contrast sensitivity was also reduced in proportion to the age. CONCLUSIONS: The amplitude of apparent accommodation in eyes with a monofocal IOL decreases significantly in proportion to age, resulting in worsening of best-corrected intermediate and near visual acuities.

Outcomes of surgery for posterior polar cataract.

PURPOSE: To report the preferred technique and the outcomes of surgery for posterior polar cataract. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: Medical records of 28 eyes of 20 consecutive patients with posterior polar cataract who had cataract surgery were reviewed. The surgical techniques used, intraoperative complications, preoperative and postoperative visual acuities, and the causes of impaired visual acuity after surgery were examined. RESULTS: Of the 28 eyes, 25 (89.3%) with a small to medium posterior polar opacity had standard phacoemulsification or aspiration surgery. Two eyes (7.1%) with a large opacity and soft lens nucleus had pars plana lensectomy, and 1 eye (3.6%) with a large opacity and hard nucleus had intracapsular cataract extraction. Among the eyes having phacoemulsification or aspiration surgery, posterior capsule rupture occurred in 2 (7.1%). The mean visual acuity improved significantly after surgery (P <.0001); however, the postoperative visual acuity was worse than 20/20 in 7 eyes (25.0%). The cause of the low acuity was amblyopia in 4 eyes (14.3%), impaired foveal function after retinal detachment in 2 eyes (7.1%), and macular degeneration in 1 eye (3.6%). CONCLUSION: Posterior polar cataracts can be safely extracted if the appropriate surgical technique is selected. Visual acuity improved significantly in most cases, although some patients with a unilateral cataract had previously developed amblyopia.

Elapsed time for capsular apposition to intraocular lens after cataract surgery.

OBJECTIVE: To examine when the anterior and posterior lens capsule completely become apposed to optics of silicone and acrylic intraocular lenses (IOLs) implanted after cataract surgery and to determine whether the different IOL materials influence the timing of completion of capsular contact. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Seventy eyes of 70 patients who were scheduled to undergo cataract surgery were randomly assigned to two groups using random number tables based on the type of IOL implanted: silicone or acrylic. Thirty-two patients in each group completed the follow-up. INTERVENTION: All eyes underwent phacoemulsification surgery with implantation of either a silicone or acrylic IOL. All IOLs were accurately placed into the capsular bag. MAIN OUTCOME MEASURES: Contact of the anterior and posterior lens capsule with the IOL optic surface was evaluated using the Scheimpflug videophotography system at 3, 5, 7, 9, 11, 14, 21, and 28 days after surgery. The postoperative day at which each capsule was completely apposed to the IOL optic was determined. In addition, anterior chamber depth was also measured. RESULTS: The anterior capsule was in contact with the IOL optic on the same day or earlier than the posterior capsule in all patients. Complete apposition of the IOL was observed significantly earlier with silicone IOLs than with acrylic IOLs with both the anterior capsule (6.2 versus 3.6 postoperative days; P < 0.0001) and the posterior capsule (11.1 versus 7.4 postoperative days; P = 0.0339). No significant change in mean anterior chamber depth was observed with the silicone IOL, whereas there was significant anterior shift after implantation of the acrylic IOL. CONCLUSIONS: Capsular contact with the IOL optic is completed within approximately 8 days after cataract surgery with silicone IOLs and 11 days with acrylic IOLs. Complete apposition to both the anterior and posterior capsule was significantly earlier with silicone IOLs than with acrylic IOLs.

Posterior capsule opacification after cataract surgery in patients with diabetes mellitus.

PURPOSE: To examine the degree of posterior capsule opacification (PCO) after cataract surgery in patients with diabetes and in nondiabetic age-matched control patients. DESIGN: Case-control study. METHODS: The PCO density value in 100 consecutive diabetic patients and in 100 nondiabetic age-matched control patients who underwent cataract surgery was measured using a Scheimpflug videophotography system at 1 week and at 3, 6, 12, 18, 24, 30, and 36 months after surgery. The incidence of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy was also evaluated. Furthermore, the stage of diabetic retinopathy and systemic condition of the diabetes were correlated with the degree of PCO. RESULTS: No significant difference between the two groups was observed in the mean value of the PCO for up to 12 months after cataract surgery. However, at 18 months and later, the PCO value in the diabetic group increased significantly and was significantly greater than in the control group. Kaplan-Meier survival curves showed that diabetic patients were significantly more likely to require Nd:YAG capsulotomy than control patients (P =.0139, Mantel-Cox log rank test). Among the diabetic patients, there was no significant correlation of PCO value with the stage of retinopathy. Furthermore, type of treatment, duration of diabetes, and hemoglobin A(1C) did not correlate with the PCO value. CONCLUSIONS: Diabetic patients developed significantly greater PCO after cataract surgery than did nondiabetic patients, but among the diabetics, the stage of diabetic retinopathy and systemic status of the diabetes did not correlate with the degree of PCO.