Proteomic changes of vitreous from rhegmatogenous retinal detachment combined with choroidal detachment using data-independent acquisition_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Pingping ^1,2 , Han Mengyao ¹ , Zhang Rui ¹ , Chen Fangyu ¹ , Li Yanzi ¹ , Yuan Jing ¹ ,  Ma Ning ¹ , Li Zhaohui ¹ , Li Lu ² , Wu Jianhua ¹

1. Aier Eye Hospital of Wuhan University, Wuhan 410070, China;
2. Department of Eye Center, Renmin Hospital of Wuhan University, Wuhan 410070, China;

Corresponding author：

Ma Ning, Email: wjheye@163.com

Keywords：

Rhegmatogenous retinal detachment; Choroidal detachment; Vitreous; Proteomic

DOI：

10.3760/cma.j.cn511434-20240528-00210

Video：

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Objective To observe the proteomic changes in vitreous fluid samples from patients with rhegmatogenous retinal detachment combined with choroidal detachment (RRDCD). Methods A prospective cross-sectional clinical study. Vitreous fluid samples were collected from 35 patients with RRDCD (RRDCD group) and 40 patients with rhegmatogenous retinal detachment (RRD group) who were diagnosed at Wuhan Aier Eye Hospital between November 2021 and December 2023. Prior to vitrectomy, 0.3-0.5 μl of vitreous fluid was collected from the affected eyes. Differentially expressed proteins were analyzed using Data-Independent Acquisition (DIA). Three of these proteins were randomly selected for validation using enzyme-linked immunosorbent assay (ELISA). Bioinformatics analyses, including gene ontology functional enrichment and kyoto encyclopedia of genes and genomes pathway enrichment, were performed to explore the functions of the differentially expressed proteins. Results Significant differences were observed between the RRDCD and RRD groups in intraocular pressure (t=－12.795), the number of retinal tears (t=4.601), the extent of retinal detachment (χ²=39.642), axial length (t=0.840), postoperative proliferative vitreoretinopathy incidence (χ²=4.730), single-surgery reattachment rate (χ²=7.717), and best-corrected visual acuity (t=7.033) at 6 months postoperatively (P＜0.05). A total of 237 differentially expressed proteins were identified between the RRDCD and RRD groups, with 63 upregulated and 174 downregulated. These proteins were involved in pathways such as extracellular matrix-receptor interaction, complement activation, coagulation, and lysosomal pathways. ELISA validation results showed that the expression trends of the three selected proteins in the RRDCD and RRD groups were consistent with the DIA proteomic analysis. Compared to the RRD group, proteins such as fibrin, coagulation factors, cathepsins, and trypsin inhibitors were significantly upregulated in the RRDCD group. Conclusions The protein expression profile in vitreous fluid samples from RRDCD patients show significant alterations compared to the RRD group. These differential changes suggest that RRDCD is closely associated with complement and coagulation cascade activation, lysosomal pathways, and extracellular matrix remodeling.

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14.	Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis[J]. Nat Rev Mol Cell Biol, 2020, 21(2): 101-118. DOI: 10.1038/s41580-019-0185-4.
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24.	Nikitovic D, Papoutsidakis A, Karamanos NK, et al. Lumican affects tumor cell functions, tumor-ECM interactions, angiogenesis and inflammatory response[J]. Matrix Biol, 2014, 35: 206-214. DOI: 10.1016/j.matbio.2013.09.003.
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27.	Grafe I, Yang T, Alexander S, et al. Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta[J]. Nat Med, 2014, 20(6): 670-675. DOI: 10.1038/nm.3544.
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1. Adelman RA, Parnes AJ, Michalewska Z, et al. Clinical variables associated with failure of retinal detachment repair: the European vitreo-retinal society retinal detachment study report number 4[J]. Ophthalmology, 2014, 121(9): 1715-1719. DOI: 10.1016/j.ophtha.2014.03.012.
2. Yu Y, An M, Mo B, et al. Risk factors for choroidal detachment following rhegmatogenous retinal detachment in a chinese population[J]. BMC Ophthalmol, 2016, 6: 140. DOI: 10.1186/s12886-016-0319-9.
3. Kang JH, Park KA, Shin WJ, et al. Macular hole as a risk factor of choroidal detachment in rhegmatogenous retinal detachment[J]. Korean J Ophthalmol, 2008, 22(2): 100-103. DOI: 10.3341/kjo.2008.22.2.100.
4. Sharma T, Gopal L, Badrinath SS. Primary vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment[J]. Ophthalmology, 1998, 105(12): 2282-2285. DOI: 10.1016/s0161-6420(98)91230-1.
5. Jarrett WH 2nd. Rhematogenous retinal detachment complicated by severe intraocular inflammation, hypotony, and choroidal detachment[J]. Trans Am Ophthalmol Soc, 1981, 79: 664-683.
6. Ye Z, Vakhrushev SY. The role of data-independent acquisition for glycoproteomics[J/OL]. Mol Cell Proteomics, 2021, 20: 100042[2021-01-07]. https://pubmed.ncbi.nlm.nih.gov/33372048/. DOI: 10.1074/mcp.R120.002204.
7. Luo S, Xu H, Yang L, et al. Quantitative proteomics analysis of human vitreous in rhegmatogenous retinal detachment associated with choroidal detachment by data-independent acquisition mass spectrometry[J]. Mol Cell Biochem, 2022, 477(6): 1849-1863. DOI: 10.1007/s11010-022-04409-0.
8. Takahashi S, Adachi K, Suzuki Y, et al. Profiles of inflammatory cytokines in the vitreous fluid from patients with rhegmatogenous retinal detachment and their correlations with clinical features[J/OL]. Biomed Res Int, 2016, 2016: 4256183[2016-12-15]. https://pubmed.ncbi.nlm.nih.gov/28074184/. DOI: 10.1155/2016/4256183.
9. Roybal CN, Velez G, Toral MA, et al. Personalized proteomics in proliferative vitreoretinopathy implicate hematopoietic cell recruitment and mTOR as a therapeutic target[J]. Am J Ophthalmol, 2018, 186: 152-163. DOI: 10.1016/j.ajo.2017.11.025.
10. Gao BB, Chen X, Timothy N, et al. Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy[J]. J Proteome Res, 2008, 7(6): 2516-2525. DOI: 10.1021/pr800112g.
11. Zayit-Soudry S, Moroz I, Loewenstein A. Retinal pigment epithelial detachment[J]. Surv Ophthalmol, 2007, 52(3): 227-243. DOI: 10.1016/j.survophthal.2007.02.008.
12. Tabor SJ, Yuda K, Deck J, et al. Retinal injury activates complement expression in Müller cells leading to neuroinflammation and photoreceptor cell death[J]. Cells, 2023, 12(13): 1754. DOI: 10.3390/cells12131754.
13. Zhang Z, Yue P, Lu T, et al. Role of lysosomes in physiological activities, diseases, and therapy[J]. J Hematol Oncol, 2021, 14(1): 79. DOI: 10.1186/s13045-021-01087-1.
14. Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis[J]. Nat Rev Mol Cell Biol, 2020, 21(2): 101-118. DOI: 10.1038/s41580-019-0185-4.
15. Yang C, Wang X. Lysosome biogenesis: regulation and functions[J/OL]. J Cell Biol, 2021, 220(6): e202102001[2021-06-07]. https://pubmed.ncbi.nlm.nih.gov/33950241/. DOI: 10.1083/jcb.202102001.
16. Naumnik W, Ossolińska M, Płońska I, et al. Endostatin and cathepsin-V in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis[J]. Adv Exp Med Biol, 2015, 833: 55-61. DOI: 10.1007/5584_2014_26.
17. Huang K, Gao L, Yang M, et al. Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-induced hypertrophy[J]. Int J Biochem Cell Biol, 2017, 89: 6-15. DOI: 10.1016/j.biocel.2017.05.020.
18. Coppini LP, Visniauskas B, Costa EF, et al. Corneal angiogenesis modulation by cysteine cathepsins: in vitro and in vivo studies[J]. Exp Eye Res, 2015, 134: 39-46. DOI: 10.1016/j.exer.2015.03.012.
19. Gabison E, Chang JH, Hernández-Quintela E, et al. Anti-angiogenic role of angiostatin during corneal wound healing[J]. Exp Eye Res, 2004, 78(3): 579-589. DOI: 10.1016/j.exer.2003.09.005.
20. Punturieri A, Filippov S, Allen E, et al. Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages[J]. J Exp Med, 2000, 192(6): 789-799. DOI: 10.1084/jem.192.6.789.
21. Vidak E, Javoršek U, Vizovišek M, et al. Cysteine cathepsins and their extracellular roles: shaping the microenvironment[J]. Cells, 2019, 8(3): 264. DOI: 10.3390/cells8030264.
22. Santos FM, Gaspar LM, Ciordia S, et al. iTRAQ quantitative proteomic analysis of vitreous from patients with retinal detachment[J]. Int J Mol Sci, 2018, 19(4): 1157. DOI: 10.3390/ijms19041157.
23. Arndt C, Hubault B, Hayate F, et al. Increased intravitreal glucose in rhegmatogenous retinal detachment[J]. Eye (Lond), 2023, 37(4): 638-643. DOI: 10.1038/s41433-022-01968-w.
24. Nikitovic D, Papoutsidakis A, Karamanos NK, et al. Lumican affects tumor cell functions, tumor-ECM interactions, angiogenesis and inflammatory response[J]. Matrix Biol, 2014, 35: 206-214. DOI: 10.1016/j.matbio.2013.09.003.
25. Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer[J]. EMBO Rep, 2014, 15(12): 1243-1253. DOI: 10.15252/embr.201439246.
26. Su J, Haner CV, Imbery TE, et al. Reelin is required for class-specific retinogeniculate targeting[J]. J Neurosci, 2011, 31(2): 575-586. DOI: 10.1523/jneurosci.4227-10.2011.
27. Grafe I, Yang T, Alexander S, et al. Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta[J]. Nat Med, 2014, 20(6): 670-675. DOI: 10.1038/nm.3544.
28. Sottile J. Regulation of angiogenesis by extracellular matrix[J]. Biochim Biophys Acta, 2004, 1654(1): 13-22. DOI: 10.1016/j.bbcan.2003.07.002.
29. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system[J]. Nat Med, 2003, 9(6): 677-684. DOI: 10.1038/nm0603-677.
30. Karagiannis ED, Popel AS. Identification of novel short peptides derived from the alpha 4, alpha 5, and alpha 6 fibrils of type IV collagen with anti-angiogenic properties[J]. Biochem Biophys Res Commun, 2007, 354(2): 434-439. DOI: 10.1016/j.bbrc.2006.12.231.
31. Creveling CJ, Alsanea Y, Coats B. Correlation of collagen fibril properties and inner limiting membrane thickness with vitreoretinal adhesion in human eyes[J/OL]. Exp Eye Res, 2022, 223: 109189[2022-07-20]. https://pubmed.ncbi.nlm.nih.gov/35868365/. DOI: 10.1016/j.exer.2022.109189.

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Latest ArticlesProteomic changes of vitreous from rhegmatogenous retinal detachment combined with choroidal detachment using data-independent acquisition

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