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Correlation Between Nuclear Cataract And Axial Myopia

Posted on:2019-05-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q ZhangFull Text:PDF
GTID:1314330542482573Subject:Ophthalmology
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Patients with myopia often develop nuclear cataracts.However,unlike agerelated cataracts and cortical cataracts,this type of cataract appears earlier and produces a more pronounced visual axis.With the high incidence of myopia in China,it is a problem that needs to be faced and solved the near future.Researchers have explored the causal relationship between high myopia and cataract from a pathomorphological aspect.However,the difference between axial myopia and refractive myopia is often overlooked,which results in the interference of refractive myopia in the research results.The study of its pathogenesis needs further study and analysis.The research presented in this article is based on the change of the foveal position in relation to the change of the visual axis in axial myopia.The study is divided into two parts,where the intimate relationship between nuclear cataract and axial myopia is preliminarily discussed.Objective1.To detect the distance between the fovea and the ONH center(d MO),the vertical distance between the fovea and the horizontal line pass of the ONH center(d MOv),and the horizontal distance between the fovea and the vertical line pass of the ONH center(d MOh)through clinical imaging analyses to investigate the change in the foveal position in patients with different axial lengths.2.To detect the distance between the fovea and the ONH center(d MO),the vertical distance between the fovea and the horizontal line pass of the ONH center(d MOv),and the horizontal distance between the fovea and the vertical line pass of the ONH center(d MOh)through clinical imaging analyses to investigate the effect of these indicators on nuclear cataract—to further study the correlation between axial myopia and nuclear cataract.3.To use proteomics technology to screen and identify relevant proteins in the aqueous humor of healthy controls,nuclear cataract patients,and patients with axial myopia—verifying the reliability of iTRAQ proteomics and the applicability of mass spectrometry techniques.4.To compare the proteins in the aqueous humor of healthy controls,nuclear cataract patients,and patients with axial myopia,in addition to screening and identifying proteins associated with axial myopia complicated by nuclear cataracts.This will act as a theoretical basis for the further discovery of new targets and explore the complications of cataract prevention in high myopia.Methods 1.The effect of nuclear cataract on the position of the fovea in patients with axial myopia i.Changes in the position of the fovea in myopia patients with different axial lengthsA total of 186 samples from 96 high myopia patients were selected.The age range ranged from 18 to 81 years old,with a mean of 41.53±18.14 years.The spherical equivalent ranged from-6.00 to-31.50 D,with an average of-12.60±6.00 D.The axial length ranged from 24.75-26.10 mm,with a mean of 28.76 ±2.61 mm.The groups were determined by axial length: ?26mm as AL1 with 26 eyes,26.01mm~?28mm as AL2 with 49 eyes,28.01mm~ ?30mm as AL3 with 38 eyes,and >30mm as AL4 with 73 eyes.Using DRI-OCT Atlantis,fundus imaging,and IOL Master,three indices were measured: the distance between the fovea and the optic nerve head(ONH)center(d MO),the vertical distance between the fovea and the horizontal line pass of the ONH center(d MOv),and the horizontal distance between the fovea and the vertical line pass of the ONH center(d MOh)to conduct further statistical analyses.Changes in the position of the fovea in differently aged myopia patients A total of 126 samples from 63 high myopia patients were selected.The age ranged from 18 to 81 years,with a mean of 58.21±10.79 years.The spherical equivalent ranged from-6.00 to-31.50 D,with an average of-10.91±5.53.The axial length ranged from 24.75-26.10 mm,with a mean of 28.23 ±3.04 mm.According to the presence or absence of nuclear cataract,the samples were divided into 2 groups: Age 2 group was comprised of samples with no nuclear cataract,with 36 eyes;Age 3 group included samples with nuclear cataract,with 90 eyes.Images were collected using DRI-OCT Atlantis,fundus imaging,and IOL Master,and the patients' d MO,d MOv,and d MOh were measured and statistically analyzed.2.Lens proteomics in patients with nuclear cataract and axial myopiai.Validation of protein samplesThe aqueous humor of 25 patients with or without nuclear cataract or axial myopia were collected and divided into 3 groups: Group A(nuclear cataract,normal axial length)of 5 cases with a mean age of 79.3±4.9 years and average axial length of 23.0±0.4mm;Group B(nuclear cataract,axial myopia)of 9 cases with a mean age of 80.8±4.1 years and an average axial length of 28.5±1.5mm;Group C(no cataract,axial myopia)of 11 cases with a mean age of 21.1±10.5 years and an average axial length of 30.1±7.9mm.8 samples were randomly sampled: 2 from Group A,3 from Group B,and 3 from Group C.Western-Blot protein quantification and iTRAQ analyses were performed.ii.Quantifying the effect of proteins using high-performance liquid chromatog-raphy and iTRAQ combined with tandem mass spectrometry 25 samples of the aqueous humor were subjected to lysis and enzymolysis,as well as isobaric iTRAQ labeling(113,114,115,116,117,118,119,and 121)to qualitatively and quantitatively analyze,identify,and quantify proteins using high-resolution chromat-ography.Identification and screening of differential proteins in the aqueous humor of patients of different axial lengths with nuclear cataract using high-performance liquid chromatography and iTRAQ combined with tandem mass spectrometry 14 of the 25 aqueous humor samples were split into groups after isobaric iTRAQ labeling: Group A(nuclear cataract,normal axial length)of 5 cases with a mean age of 79.3±4.9 years and average axial length of 23.0±0.4mm;Group B(nuclear cataract,axial myopia)of 9 cases with a mean age of 80.8±4.1 years and an average axial length of 28.5±1.5mm.The protein obtained was quantified and subjected to comparative analyses to select for proteins with significance.iv.Identification and screening of differential proteins in the aqueous humor of patients with axial myopia and nuclear cataract using high-performance liquid chromatography and iTRAQ combined with tandem mass spectrometry 20 of the 25 aqueous humor samples were split into groups after isobaric iTRAQ labeling: Group B(nuclear cataract,axial myopia)of 9 cases with a mean age of 80.8±4.1 years and an average axial length of 28.5±1.5mm;Group C(no cataract,axial myopia)of 11 cases with a mean age of 51.1±10.5 years and an average axial length of 30.1±7.9mm.The protein obtained was quantified and subjected to comparative analyses to select for proteins with significance.Results1.Although there was an increase in d MOv in the AL2,AL3,and AL4 groups compared with the AL1 group,there were no significant differences in the change of the foveal position in patients with different types of myopia.2.The d MOv of the Age 3 group increased compared to that of the Age 2 group;the difference was statistically significant.In our best to avoid cases of refractive myopia,the position of the fovea shifted in the vertical direction in patients with axial myopia and nuclear cataract.3.The protein verification experiments performed on the 8 randomly selected samples of the aqueous humor demonstrated that the samples were normal,had adequate protein levels,was of good quality,and could be further analyzed by high performance liquid chromatography.4.Comparison of the protein expression levels of the 25 samples using highperformance liquid chromatography and iTRAQ combined with tandem mass spectrometry resulted in the ultimate identification of 918 proteins.5.Comparison of the groups resulted in the identification of 74 kinds of proteins according to different axial lengths from Group A(5 cases)and B(9 cases).Among them,B/A regulated 4 types of proteins: 0A140TA29(Complement C4-B),A0A0M3KKW6(Fab Hu 15C1 Heavy chain fragment),A0A0F7T6Q1(IGHV1-2 protein),and P19827(Inter-alpha-trypsin inhibitor heavy chain H1).They are highly expressed in Group B,despite being less expressed in Group A.B/A down-regulated 70 kinds of proteins,namely the low expression of Group B and the high expression of Group A—among which 19 species had a p-value less than 0.01.There were 2 pvalues less than 0.001: A8K5N5(c DNA FLJ78142)and V9HWE9(Epididymis secretory protein Li 22).6.Analysis of the groups resulted in the identification of a total of 186 kinds of proteins in Groups B and C.Among them,B/C was up-regulated by 39 types—namely A2RRD8(Zinc finger protein 320),which showed the greatest difference in protein expression,with a ratio of approximately 5.4.However,there were no statistically significant proteins among the 147 B/C down-regulated proteins.Yet,there were 2 proteins with p-values < 0.0001: A0A0K0K1J1(Cystatin cysteine protease)and A6XND5(Ribonuclease T2).Discussion1.There was no significant difference in the foveal position in myopic patients with different axial lengths.Therefore,the foveal position can be used as a stable constant and indicator for axial myopia to avoid interference of refractive myopia.2.The difference between the d MOv of patients with both axial myopia and nuclear cataract and patients with simple axial myopia was statistically significant.Thus,the presence of nuclear cataract in patients with axial myopia will result in the foveal position shifting in the vertical direction.3.High-performance liquid chromatography and iTRAQ combined with tandem mass spectrometry is a highly effective means to identify,quantify,and screen proteins in the aqueous humor.It has good clinical prospects for future ophthalmology studies that require samples that are difficult to obtain.Using isobaric iTRAQ labeling combined with mass spectrometry,918 proteins in the aqueous humor were identified.In a comparison of patients with nuclear cataract and axial myopia,240 differential proteins were screened—among which there were 8 significant proteins: 0A140TA29(Complement C4-B),A0A0M3KKW6(Fab Hu 15C1 Heavy chain fragment),A0A0F7T6Q1(IGHV1-2 protein),P19827(Inter-alpha-trypsin inhibitor heavy chain H1),A8K5N5(c DNA FLJ78142),V9HWE9(Epididymis secretory protein Li 22),A0A0K0K1J1(Cystatin cysteine protease),and A6XND5(Ribonuclease T2).These significant proteins are mainly involved in the immune system,as well as oxidative damage and the induction of developmental systems—providing a reliable and objective source of information for the further investigation of pathogenic genes or the discovery of predisposing factors.
Keywords/Search Tags:Nuclear cataract, axial myopia, foveal position, myopic maculopathy, iTRAQ, proteomics
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