Abstract
Eye injuries due to corneal abrasions, chemical spills, penetrating wounds, and microbial infections cause corneal scarring and opacification that result in impaired vision or blindness. However, presently available eye drop formulations of anti-inflammatory and antibiotic drugs are not effective due to their rapid clearance from the ocular surface or due to drug-related side effects such as cataract formation or increased intraocular pressure. In this article, we presented the development of a dextran sulfate-based polymer wafer (DS-wafer) for the effective modulation of inflammation and fibrosis and demonstrated its efficacy in two corneal injury models: corneal abrasion mouse model and alkali induced ocular burn mouse model. The DS-wafers were fabricated by the electrospinning method. We assessed the efficacy of the DS-wafer by light microscopy, qPCR, confocal fluorescence imaging, and histopathological analysis. These studies demonstrated that the DS-wafer treatment is significantly effective in modulating corneal inflammation and fibrosis and inhibited corneal scarring and opacification compared to the unsulfated dextran-wafer treated and untreated corneas. Furthermore, these studies have demonstrated the efficacy of dextran sulfate as an anti-inflammatory and antifibrotic polymer therapeutic.
Highlights
The cornea is an outermost part of the eye and functions as a protective barrier.It is inherently devoid of blood vessels and maintains corneal transparency, which is pertinent to its primary function of transmitting light to the back of the eye [1]
This study revealed that the Dextran sulfate (DS)-wafer downregulated the expression levels of proinflammatory IL-6, macrophages secrete inflammatory protein-1α (MIP-1α) (CCL3), and tumor necrosis factor-α (TNF-α) compared to the untreated ocular burn burn (OB) corneas
Multivalency of the the polymer polymer therapeutic therapeutic enables enables it it to to simultaneously simultaneously bind bind to to several several cell cell molecules compared to monovalent monovalent small molecular drugs
Summary
The cornea is an outermost part of the eye and functions as a protective barrier It is inherently devoid of blood vessels and maintains corneal transparency, which is pertinent to its primary function of transmitting light to the back of the eye [1]. Physical assaults such as abrasion, penetrating wounds, and chemical burns to the ocular surface disrupt the balance between anti-inflammatory and proinflammatory responses, triggering neovascularization in the cornea, scarring, and opacification [2,3]. The inflammatory process is triggered in response to injury, infection, and other insults, by the activated macrophages in the area of injury to initiate the recruitment of immune cells (neutrophils, monocytes, and lymphocytes). Immune cells play a crucial role during the initial inflammatory phase of the acute wound healing process by secreting cytokines
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