Modulation of Extracellular Matrix Composition and Chronic Inflammation with Pirfenidone Promotes Scar Reduction in Retinal Wound Repair.
Laura JahnkeVirginie PerrenoudSouska ZandiYuebing LiFederica Maria ConederaVolker EnzmannPublished in: Cells (2024)
Wound repair in the retina is a complex mechanism, and a deeper understanding of it is necessary for the development of effective treatments to slow down or even prevent degenerative processes leading to photoreceptor loss. In this study, we harnessed a laser-induced retinal degeneration model (532-nm laser photocoagulation with 300 μm spot size, 60 ms duration and 60 mV pulse), enabling a profound molecular elucidation and a comprehensive, prolonged observation of the wound healing sequence in a murine laser-induced degeneration model (C57BL/6J mice, 6-12 weeks) until day 49 post-laser. Our observations included the expression of specific extracellular matrix proteins and myofibroblast activity, along with an analysis of gene expression related to extracellular matrix and adhesion molecules through RNA measurements. Furthermore, the administration of pirfenidone (10 mg/kg via drinking water), an anti-inflammatory and anti-fibrotic compound, was used to modulate scar formation after laser treatment. Our data revealed upregulated collagen expression in late regenerative phases and sustained inflammation in the damaged tissue. Notably, treatment with pirfenidone was found to mitigate scar tissue formation, effectively downregulating collagen production and diminishing the presence of inflammatory markers. However, it did not lead to the regeneration of the photoreceptor layer.
Keyphrases
- extracellular matrix
- wound healing
- idiopathic pulmonary fibrosis
- drinking water
- diabetic retinopathy
- gene expression
- stem cells
- poor prognosis
- pulmonary fibrosis
- blood pressure
- anti inflammatory
- optical coherence tomography
- optic nerve
- multiple sclerosis
- dna methylation
- mass spectrometry
- ms ms
- mesenchymal stem cells
- long non coding rna
- metabolic syndrome
- binding protein
- combination therapy
- escherichia coli
- systemic sclerosis
- cell therapy
- health risk assessment
- insulin resistance
- skeletal muscle
- deep learning
- heavy metals
- transforming growth factor
- single molecule
- epithelial mesenchymal transition
- biofilm formation
- amino acid
- artificial intelligence
- risk assessment
- pseudomonas aeruginosa
- adipose tissue