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Characterization of extracellular matrix deposited by segmental trabecular meshwork cells.
Raghunathan, VijayKrishna; Nartey, Andrews; Dhamodaran, Kamesh; Baidouri, Hasna; Staverosky, Julia A; Keller, Kate E; Zientek, Keith; Reddy, Ashok; Acott, Ted; Vranka, Janice A.
Afiliación
  • Raghunathan V; Department of Basic Sciences, College of Optometry, University of Houston, Houston, TX, USA. Electronic address: raghunathanvijaykrishna@gmail.com.
  • Nartey A; Department of Basic Sciences, College of Optometry, University of Houston, Houston, TX, USA.
  • Dhamodaran K; Department of Basic Sciences, College of Optometry, University of Houston, Houston, TX, USA.
  • Baidouri H; Department of Basic Sciences, College of Optometry, University of Houston, Houston, TX, USA.
  • Staverosky JA; Ophthalmology and Visual Sciences, Casey Eye Institute, USA.
  • Keller KE; Ophthalmology and Visual Sciences, Casey Eye Institute, USA.
  • Zientek K; Proteomics Shared Resources, Oregon Health & Science University, Portland, OR, USA.
  • Reddy A; Proteomics Shared Resources, Oregon Health & Science University, Portland, OR, USA.
  • Acott T; Ophthalmology and Visual Sciences, Casey Eye Institute, USA.
  • Vranka JA; Ophthalmology and Visual Sciences, Casey Eye Institute, USA.
Exp Eye Res ; 234: 109605, 2023 09.
Article en En | MEDLINE | ID: mdl-37506755
PURPOSE: Biophysical and biochemical attributes of the extracellular matrix are major determinants of cell fate in homeostasis and disease. Ocular hypertension and glaucoma are diseases where the trabecular meshwork tissue responsible for aqueous humor egress becomes stiffer accompanied by changes in its matrisome in a segmental manner with regions of high or low flow. Prior studies demonstrate these alterations in the matrix are dynamic in response to age and pressure changes. The underlying reason for segmentation or differential response to pressure and stiffening are unknown. This is largely due to a lack of appropriate models (in vitro or ex vivo) to study this phenomena. METHODS: Primary trabecular meshwork cells were isolated from segmental flow regions, and cells were cultured for 4 weeks in the presence or absence or dexamethasone to obtain cell derived matrices (CDM). The biomechanical attributes of the CDM, composition of the matrisome, and incidence of crosslinks were determined by atomic force microscopy and mass spectrometry. RESULTS: Data demonstrate that matrix deposited by cells from low flow regions are stiffer and exhibit a greater number of immature and mature crosslinks, and that these are exacerbated in the presence of steroid. We also show a differential response of high or low flow cells to steroid via changes observed in the matrix composition. However, no correlations were observed between elastic moduli and presence or absence of mature and immature crosslinks in the CDMs. CONCLUSION: Regardless of a direct correlation between matrix stiffness and crosslinks, we observed distinct differences in the composition and mechanics of the matrices deposited by segmental flow cells. These results suggest distinct differences in cellular identify and likely a basis for mechanical memory post isolation and culture. Nevertheless, we conclude that although a mechanistic basis for matrix stiffness was undetermined in this study, it is a viable tool to study cell-matrix interactions and further our understanding of trabecular meshwork pathobiology.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glaucoma / Hipertensión Ocular Límite: Humans Idioma: En Revista: Exp Eye Res Año: 2023 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glaucoma / Hipertensión Ocular Límite: Humans Idioma: En Revista: Exp Eye Res Año: 2023 Tipo del documento: Article