Candidate Genes Identification and RNA-seq Based Pathway Analysis Associated with Primary Angle-closure Glaucoma with Cataract

Overview

Journal BMC Ophthalmol

Publisher Biomed Central

Specialty Ophthalmology

Date 2023 May 2

PMID 37131205

Authors

Min Liu

Fei Hu

Caifeng Lei

Min Fu

Xue Li

Ling Yu

Affiliations

Soon will be listed here.

Abstract

Background: Cataract is commonly observed in patients with primary angle-closure glaucoma; however, its underlying pathological mechanisms remain unclear. This study aimed to improve our knowledge on the pathological processes involved in primary angle-closure glaucoma (PACG) by identifying potential prognostic genes associated with cataract progression.

Methods: Thirty anterior capsular membrane samples were collected from PACG patients with cataracts and age-related cataracts. Differentially expressed genes (DEGs) between these two cohorts were analyzed using high-throughput sequencing. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to screen the DEGs, and potential prognostic markers and their coexpression network were then predicted by bioinformatic analyses. The DEGs were further validated by reverse transcription-quantitative polymerase chain reaction.

Results: A total of 399 DEGs were found to be specifically associated with cataracts development in PACG patients, among which 177 and 221 DEGs were upregulated and downregulated, respectively. STRING and Cytoscape network analyses revealed seven genes-CTGF, FOS, CAV1, CYR61, ICAM1, EGR1, and NR4A1-that were remarkably enriched and mainly involved in the MAPK, PI3K/Akt, Toll-like receptor, and TNF signaling pathways. RT-qPCR-based validation further confirmed that the sequencing results were accurate and reliable.

Conclusions: Herein, we identified seven genes and their signaling pathways that may contribute to cataract progression in patients with high intraocular pressure. Taken together, our findings highlight new molecular mechanisms that may explain the high incidence of cataracts in PACG patients. In addition, the genes identified herein may represent new foundations for the development of therapeutic strategies for PACG with cataract.

References

Bui T, Wiesolek H, Sumagin R . ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol. 2020; 108(3):787-799. PMC: 7977775. DOI: 10.1002/JLB.2MR0220-549R. View

. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2021; 105(Suppl 1):1-169. DOI: 10.1136/bjophthalmol-2021-egsguidelines. View

Gupta V, Awasthi N, Wagner B . Specific activation of the glucocorticoid receptor and modulation of signal transduction pathways in human lens epithelial cells. Invest Ophthalmol Vis Sci. 2007; 48(4):1724-34. PMC: 2814520. DOI: 10.1167/iovs.06-0889. View

Shu D, Ng K, Wishart T, Chui J, Lundmark M, Flokis M . Contrasting roles for BMP-4 and ventromorphins (BMP agonists) in TGFβ-induced lens EMT. Exp Eye Res. 2021; 206:108546. DOI: 10.1016/j.exer.2021.108546. View

Fan H, Suzuki T, Ogata M, Nakagawa Y, Onouchi H, Kawai K . Expression of PCNA, ICAM-1, and vimentin in lens epithelial cells of cataract patients with and without type 2 diabetes. Tokai J Exp Clin Med. 2012; 37(2):51-6. View

Ma B, Kang Q, Qin L, Cui L, Pei C . TGF-β2 induces transdifferentiation and fibrosis in human lens epithelial cells via regulating gremlin and CTGF. Biochem Biophys Res Commun. 2014; 447(4):689-95. DOI: 10.1016/j.bbrc.2014.04.068. View

Gao C, Lin X, Fan F, Liu X, Wan H, Yuan T . Status of higher TGF-β1 and TGF-β2 levels in the aqueous humour of patients with diabetes and cataracts. BMC Ophthalmol. 2022; 22(1):156. PMC: 8981924. DOI: 10.1186/s12886-022-02317-x. View

Ahmad A, Ahsan H . Biomarkers of inflammation and oxidative stress in ophthalmic disorders. J Immunoassay Immunochem. 2020; 41(3):257-271. DOI: 10.1080/15321819.2020.1726774. View

Weinreb R, Khaw P . Primary open-angle glaucoma. Lancet. 2004; 363(9422):1711-20. DOI: 10.1016/S0140-6736(04)16257-0. View

10.

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

11.

Choi S, Kim K, Perkins G, Phan S, Edwards G, Xia Y . AIBP protects retinal ganglion cells against neuroinflammation and mitochondrial dysfunction in glaucomatous neurodegeneration. Redox Biol. 2020; 37:101703. PMC: 7484594. DOI: 10.1016/j.redox.2020.101703. View

12.

Magyar M, Zsiros V, L Kiss A, Nagy Z, Szepessy Z . [The role of caveolae in cataractogenesis: examination of human lens epithelial cells]. Orv Hetil. 2019; 160(8):300-308. DOI: 10.1556/650.2019.31313. View

13.

Fernandez-Vega Cueto A, Alvarez L, Garcia M, Alvarez-Barrios A, Artime E, Fernandez-Vega Cueto L . Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications. Biology (Basel). 2021; 10(8). PMC: 8389649. DOI: 10.3390/biology10080763. View

14.

Abdelkader H, Longman M, Alany R, Pierscionek B . On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?. Oxid Med Cell Longev. 2016; 2016:3240261. PMC: 5086400. DOI: 10.1155/2016/3240261. View

15.

Chen Y, Du X . Functional properties and intracellular signaling of CCN1/Cyr61. J Cell Biochem. 2006; 100(6):1337-45. DOI: 10.1002/jcb.21194. View

16.

Feng G, Zhang Z, Dang M, Zhang X, Doleyres Y, Song Y . Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration. Biomaterials. 2017; 131():86-97. PMC: 5448136. DOI: 10.1016/j.biomaterials.2017.03.029. View

17.

Liu C, Lee T, Chen Y, Liang C, Wang S, Lue J . PM-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway. Part Fibre Toxicol. 2018; 15(1):4. PMC: 5767014. DOI: 10.1186/s12989-018-0240-x. View

18.

Tie J, Chen D, Guo J, Liao S, Luo X, Zhang Y . Transcriptome-wide study of the response of human trabecular meshwork cells to the substrate stiffness increase. J Cell Biochem. 2020; 121(5-6):3112-3123. DOI: 10.1002/jcb.29578. View

19.

Lee S, Lin S, Li M, Liang R . Possible mechanism of exacerbating cataract formation in cataractous human lens capsules induced by systemic hypertension or glaucoma. Ophthalmic Res. 1997; 29(2):83-90. DOI: 10.1159/000268001. View

20.

Sacca S, Vernazza S, Iorio E, Tirendi S, Bassi A, Gandolfi S . Molecular changes in glaucomatous trabecular meshwork. Correlations with retinal ganglion cell death and novel strategies for neuroprotection. Prog Brain Res. 2020; 256(1):151-188. DOI: 10.1016/bs.pbr.2020.06.003. View