| Objective:(1) Bone morphogenetic proteins (BMPs) are multi-functional cytokines that have wide ranging effects on a variety of tissues. The aims of this study were to clarify the role of BMPs in sclera remodeling by examining sclera of human, rat and guinea pigs for BMP-2 to BMP-7 to study if their was any change during myopia induction in guinea pigs sclera, and then by cell culture in vitro to make clear the effect of BMP-2 on sclera fibroblasts differentiation, proliferation, its effect on scleral collagen and proteoglycans which are the main composition of ECM and its possible signal pathway. (2) To evaluate the visual performance of high myopia patients with diffractive multifocal intraocular lens (MIOL) as compared with aspherical monofocal intraocular lens (IOL). Methods:(1) First the expression of BMPs and BMPs receptors in human, guinea pig and rat posterior sclera were detected using reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence. Then two-week-old guinea pigs were monocularly form-deprived with a translucent headgear. After fourteen days induction of form deprivation myopia (FDM), total RNA was isolated and subjected to RT-PCR for the expression of BMPs and BMP receptors in tissues from the posterior sclera. Western blotting analysis was used to investigate changes in protein expression for BMPs. Levels of BMPs mRNA as well as protein expression were compared between FDM and contralateral control eyes. Cells were isolated from the human sclera and treated with various doses of BMP-2 (0,1,10, 100 ng/mL). The influence of BMP-2 on cell proliferation and cell cycle was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis. Cell phenotype and activated signal pathway was investigated by indirect immunofluorescence special for a-SMA and phospho-smad 1/5/8. The protein level of phospho-smad 1/5/8 was further examined by western-blot. Reverse transcription polymerase chain reaction (RT-PCR) and western-blot were used to determine collagen type1, aggrecan mRNAs and proteins in HSF that were incubated with BMP-2. (2) A prospective nonrandomized controlled study was conducted. Consecutively 36 senile cataract patients (72 eyes) received phacoemulsification and IOL implantation,12 patients (24 eyes) were implanted with AcrySof IQ ReSTOR SN6AD3 IOL,12 patients (24 eyes) were implanted with AcrySof IQ ReSTOR SN6AD1 IOL and another 12 patients (24 eyes) were implanted with AcrySof IQ SN60WF as control group. All patients were assessed at 6 months postoperatively in these aspects:uncorrected and best corrected visual acuities for distance(5m), intermediate(60cm) and near(30cm), modulation transfer function(MTF), and defocus curve. Patient satisfaction (spectacle independence, glare or halo disturbance and overall satisfaction) was assessed by a questionnaire. Results:(1) Human sclera expresses mRNAs for BMP-2, BMP-4, BMP-5, BMP-7, BMP-RIA, BMP-RIB and BMP-RII. Conversely, rat sclera only expresses mRNA for BMP-7 and BMP-RIB, while the expression of BMPs and BMPs receptors in guinea pigs were similar to those of human. Fourteen days after the induction of myopia, we observed statistically significant decrease in mRNA expression for BMP-2 (-34.48%) and BMP-5(-23.67%) as well as in protein expression for BMP-2 (-23.42%) and BMP-5(-15.21%) in the posterior sclera of FDM-affected eyes (p<0.05 vs. contralateral control eyes). With 100 ng/ml BMP-2, cell proliferation increased significantly, cell cycle moved to S and S+G2M phases, and more cells differentiated into myofibroblast compared to normal control cells (p<0.05); A 72h incubation with 100ng/ml BMP-2 resulted in significantly increased collagen 1, aggrecan mRNA and protein expression (p<0.05). Smadl mRNA and phospho-smad 1/5/8 protein levels increased significantly in HSF incubated with 100 ng/ml BMP-2 (p<0.01). (2) At 6 months postoperatively, both uncorrected and distance corrected, intermediate, near visual acuity were significantly better in multifocal groups than control monofocal group (p<0.01). Intermediate visual acuity in SN6AD1 group was a little higher than that in SN6AD3 group (p<0.05), conversely the near visual acuity in SN6AD3 group was better than SN6AD1 group (p<0.05). MTF with a 5.0 mm aperture was similar in the three groups and there was no statistically significant difference. Patients in both multifocal groups reported excellent overall spectacle independence and satisfaction with the IOLs. Conclusions:(1) BMP-2,-4,-5 are expressed in human and guinea pig sclera. In the posterior sclera, expression of the BMP-2 and BMP-5 significantly decreased in guinea pig FDM eyes. BMP-2 can promote human sclera cell proliferation and differentiation, as well as to help extracellular matrix synthesis possibly through classical smad pathway. This finding might indicate that various BMPs act as components of the scleral cytokines regulating tissue homeostasis and provides evidence that alterations in the expression of BMP-2 and BMP-5 are associated with sclera remodeling during myopia induction. (2) Compared with aspherical monofocal IOL, AcrySof ReSTOR IQ multifocal IOLs could provide a functional vision ranged from near to distance, resulting in high level of spectacle independence and satisfaction among high myopia. |
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