2024Acta OphthalmologicaRequires access

A novel effect of plasma rich in growth factors in the small leucine‐rich proteoglycans regulation in trabecular meshwork

Susana del Olmo‐Aguado, Carla Martin Cueto, Andrés Fernández‐Vega Cueto, Ignácio Rodriguez-Uña, Nagore de Pablo Herranz, Pedro Calvo, Luis Quirós Fernández, Jesús Merayo-Llovés

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Abstract

Aims/Purpose: To analyse the effect of plasma rich in growth factors (PRGF) on the activity of small leucine‐rich proteoglycans (SRLPs) involved in extracellular matrix regulation in a trabecular meshwork fibrosis in vitro model. Methods: Trabecular meshwork cells were obtained from cadaveric donors in collaboration with the Blood and Tissue Centre of the Principality of Asturias (CEImPA2022.359). The cells were exposed to TGFβ2, which induces the expression of fibrosis markers. After 24 h in the presence of TGFβ2, the cells were treated with PRGF or human serum (control group) for 7 days. After the treatment period, samples were processed for immunocytochemistry or gene expression analysis by qPCR. Immunocytochemical techniques were used to examine the markers α‐sma, collagen I and collagen IV markers. The gene expression analysis included the genes lumican (LUM), decorin (DCN), biglycan (BGN) and fibromodulin (FMOD). Results: The induction of fibrosis in trabecular meshwork cells, characterized by an increase in extracellular matrix components such as α‐sma, collagen I and collagen IV, led to an increase in the expression of several SRLPs analysed, such as lumican, decorin, biglycan and fibromodulin. Treatment with PRGF for 7 days significantly reduced the expression of lumican, decorin and biglycan. In contrast, fibromodulin expression levels were slightly increased in the PRGF‐treated group. Conclusions: SRLPs play an important role in the regulation of the extracellular matrix in several ocular tissues. In glaucoma, altered expression of SRLPs such as lumican, decorin and biglycan leads to a glaucomatous phenotype in animal models. Changes in the expression of SRLPs have also been reported in the aqueous humour of glaucoma patients. PRGF treatment regulates the expression of SRLPs, as well as the expression and deposition of other fibrotic markers, and may promote aqueous humour flow and intraocular pressure control.

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Aims/Purpose: To analyse the effect of plasma rich in growth factors (PRGF) on the activity of small leucine‐rich proteoglycans (SRLPs) involved in extracellular matrix regulation in a trabecular meshwork fibrosis in vitro model. Methods: Trabecular meshwork cells were obtained from cadaveric donors in collaboration with the Blood and Tissue Centre of the Principality of Asturias (CEImPA2022.359). The cells were exposed to TGFβ2, which induces the expression of fibrosis markers. After 24 h in the presence of TGFβ2, the cells were treated with PRGF or human serum (control group) for 7 days. After the treatment period, samples were processed for immunocytochemistry or gene expression analysis by qPCR. Immunocytochemical techniques were used to examine the markers α‐sma, collagen I and collagen IV markers. The gene expression analysis included the genes lumican (LUM), decorin (DCN), biglycan (BGN) and fibromodulin (FMOD). Results: The induction of fibrosis in trabecular meshwork cells, characterized by an increase in extracellular matrix components such as α‐sma, collagen I and collagen IV, led to an increase in the expression of several SRLPs analysed, such as lumican, decorin, biglycan and fibromodulin. Treatment with PRGF for 7 days significantly reduced the expression of lumican, decorin and biglycan. In contrast, fibromodulin expression levels were slightly increased in the PRGF‐treated group. Conclusions: SRLPs play an important role in the regulation of the extracellular matrix in several ocular tissues. In glaucoma, altered expression of SRLPs such as lumican, decorin and biglycan leads to a glaucomatous phenotype in animal models. Changes in the expression of SRLPs have also been reported in the aqueous humour of glaucoma patients. PRGF treatment regulates the expression of SRLPs, as well as the expression and deposition of other fibrotic markers, and may promote aqueous humour flow and intraocular pressure control.

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Available abstract

Aims/Purpose: To analyse the effect of plasma rich in growth factors (PRGF) on the activity of small leucine‐rich proteoglycans (SRLPs) involved in extracellular matrix regulation in a trabecular meshwork fibrosis in vitro model. Methods: Trabecular meshwork cells were obtained from cadaveric donors in collaboration with the Blood and Tissue Centre of the Principality of Asturias (CEImPA2022.359). The cells were exposed to TGFβ2, which induces the expression of fibrosis markers. After 24 h in the presence of TGFβ2, the cells were treated with PRGF or human serum (control group) for 7 days. After the treatment period, samples were processed for immunocytochemistry or gene expression analysis by qPCR. Immunocytochemical techniques were used to examine the markers α‐sma, collagen I and collagen IV markers. The gene expression analysis included the genes lumican (LUM), decorin (DCN), biglycan (BGN) and fibromodulin (FMOD). Results: The induction of fibrosis in trabecular meshwork cells, characterized by an increase in extracellular matrix components such as α‐sma, collagen I and collagen IV, led to an increase in the expression of several SRLPs analysed, such as lumican, decorin, biglycan and fibromodulin. Treatment with PRGF for 7 days significantly reduced the expression of lumican, decorin and biglycan. In contrast, fibromodulin expression levels were slightly increased in the PRGF‐treated group. Conclusions: SRLPs play an important role in the regulation of the extracellular matrix in several ocular tissues. In glaucoma, altered expression of SRLPs such as lumican, decorin and biglycan leads to a glaucomatous phenotype in animal models. Changes in the expression of SRLPs have also been reported in the aqueous humour of glaucoma patients. PRGF treatment regulates the expression of SRLPs, as well as the expression and deposition of other fibrotic markers, and may promote aqueous humour flow and intraocular pressure control.

Key concepts: Lumican, Biglycan, Decorin, Trabecular meshwork, Extracellular matrix, Proteoglycan, Versican, Cell biology

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