Table 4.

Target gene silencing or downregulation to modulate corneal fibrosis and scarring, and their potential adverse effects and limitations.

Genes	Mechanism of Action	Risks/Potential Side Effects	Limitations of Approach
SEMA3A	siRNA-mediated downregulation of fibroblast/TGFβ-fibrotic pathways	Neuron polarization defects; corneal sensory alterations; risk of VEGF-mediated corneal neovascularization [215,216]	Variable knockdown efficiency by siRNAs and instability and degradation of siRNAs inside target cells. Lack of reliable delivery methods—transfection approach is poor for primary cells and electroporation induces cell death. Altered target gene expression induces phenotypic variations and altered cellular signaling [217].
USP-10	siRNA-mediated downregulation of immune cell infiltration and fibrosis gene expression	Altered de-ubiquitination modulates multiple cellular issues, e.g., protein stability [202]
KCa3.1	Using TRAM 34, an ion channel block to modulate Ca++-activated K+ signaling in fibroblast and MyoF activation; suppressed macrophages polarization towards M1 phenotype [165,218,219]	Affects cell growth and survival; triggers cell death [165,218,219]