Clinical Ophthalmology (Mar 2021)

Abnormal N-Glycosylation of Human Lens Epithelial Cells in Type-2 Diabetes May Contribute to Cataract Progression

  • Ramos-Martínez I,
  • Vivanco-Rojas O,
  • Juárez-Domínguez B,
  • Hernández-Zimbrón L,
  • Ochoa-de la Paz L,
  • Quiroz-Mercado H,
  • Ramírez-Hernández E,
  • Gulias-Cañizo R,
  • Zenteno E

Journal volume & issue
Vol. Volume 15
pp. 1365 – 1373

Abstract

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Ivan Ramos-Martínez,1– 3 Oscar Vivanco-Rojas,2 Brenda Juárez-Domínguez,2 Luis Hernández-Zimbrón,1,2 Lenin Ochoa-de la Paz,1,2 Hugo Quiroz-Mercado,2 Eleazar Ramírez-Hernández,1 Rosario Gulias-Cañizo,4 Edgar Zenteno1,2 1Departamento de Bioquímica, Facultad de Medicina UNAM, Ciudad de Mexico, 04510, Mexico; 2Departamento de Investigación, Asociación para Evitar la Ceguera en Mexico I.A.P. Hospital Dr. Luis Sánchez Bulnes, Mexico City, Mexico; 3Glycobiology, Cell Growth and Tissue Repair Research Unit (Gly-CRRET), Université Paris Est Créteil (UPEC), Créteil, France; 4Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac Mexico, Huixquilucan, Estado de Mexico, MexicoCorrespondence: Rosario Gulias-Cañizo; Edgar Zenteno Email [email protected]; [email protected]: In order to better understand cataract development, we analyzed the glycosylation profile of human lens epithelial cells (HLECs) from anterior lens capsules of type 2 diabetes mellitus (T2DM) and non-diabetic (ND) patients undergoing routine cataract surgery.Setting: Research Department of the Asociación para Evitar la Ceguera, Hospital “Dr. Luis Sánchez Bulnes”, Mexico.Design: Experimental study.Methods: Evaluation of anterior lens capsules from T2DM and ND patients undergoing phacoemulsification and free from other ocular diseases.Results: Hematoxylin-eosin staining revealed HLECs alterations in T2DM samples. From lectins with different sugar specificities used, concanavalin A showed significant differences, labeling homogeneously both in the cytoplasm and in cell membranes in ND capsules, while in T2DM capsules, in addition to membrane and cytoplasm labeling, there were perinuclear vesicles with high concanavalin A labeling. Two-dimensional gel electrophoresis showed that T2DM patients have a ∼ 65-kDa spot with an isoelectric point of 5.5 with a higher density compared to ND capsules, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed 62% homology with type-1 cytokeratin. Immunohistochemistry using anti-pan cytokeratin antibody revealed co-localization with concanavalin A, and a lectin blot revealed with concanavalin A showed a band of ∼ 65 kDa, a molecular weight that corresponds to human type 1 cytokeratin.Conclusion: These results suggest that over-expression of N-glycosidically linked human type 1 cytokeratin may induce capsule disruption and affect selective permeability, allowing the entry of different molecules to the lens that facilitate cataract progression.Keywords: glycosylation, human epithelial lens cells, diabetes mellitus, cataract

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