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Review
. 2025 Apr 24:12:1539542.
doi: 10.3389/fmolb.2025.1539542. eCollection 2025.

The oxidative-stress-senescence axis in keratoconus: new insights into corneal degeneration

Maria Laura Passaro #  1   2 , Michele Rinaldi #  1 , Valentina Morgera  3 , Antonia Feola  3 , Vito Romano  4 , Mario Troisi  1 , Diego Strianese  1 , Raffaele Piscopo  1 , Samantha Messina  5 , Antonella Romano  3 , Antonio Porcellini  3 , Antonio Pezone  3 , Ciro Costagliola  1
Affiliations
Review

The oxidative-stress-senescence axis in keratoconus: new insights into corneal degeneration

Maria Laura Passaro et al. Front Mol Biosci. .

Abstract

Keratoconus is a bilateral and asymmetric degenerative eye disease that causes corneal thinning and bowing, leading to irregular astigmatism and vision loss. Although environmental and genetic factors contribute to the disease's development, the exact cause and underlying pathological mechanism remain unknown. In this review, we comprehensively explore the latest pathophysiological mechanisms of keratoconus, focusing on oxidative damage and inflammation. Senescence emerges as a key driver of keratoconus pathogenesis. Understanding these common elements enhances our understanding of the disease and paves the way for innovative therapeutic approaches to keratoconus.

Keywords: antioxidant therapy; inflammation; keratoconus; mitochondrial dysfunction; oxidative stress; senescence.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Anatomy of the human eye and cornea. (A) Section of the anterior part of the human eye; (B) Section of the cornea illustrating five layers. Created with Biorender.com.
FIGURE 2
FIGURE 2
Schematic representation of cellular abnormalities in keratoconus. (A) Normal cornea structure con genetic predisposition. (B) Mechanical stretch in keratoconus enhances the expression of many protease genes in stromal cells, exacerbating ECM degradation. Additionally, aberrant differentiation of corneal epithelial cells and enhanced inflammatory signals were found. Created with BioRender.com.
FIGURE 3
FIGURE 3
The cascade of molecular processes in the pathophysiology of keratoconus. Summary of molecular involvement in the corneal layers. External causes such as eye rubbing, increased reactive oxygen species (ROS), mitochondrial damage, or gene alterations can activate biochemical cascades, causing a lack of cellular homogeneity in the corneal epithelium. There is an increase in proinflammatory cytokines (IL-6, TNF-alpha) and an exacerbation of the function of metalloproteinases (MMP-1, MMP-2, MMP-9, MMP-13), resulting in increased keratocyte apoptosis, resulting in a reduction in corneal stromal thickness, and both histological changes and disruption of the extracellular matrix. Created with Biorender.com.
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