Related Experiment Video
Updated: Aug 14, 2026
Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
The cascade hypothesis of keratoconus
M Cristina Kenney1, Donald J Brown
1Department of Ophthalmology, UCI Medical Center, University of California, Irvine, Building 55, Room 220, 101 The City Drive, Orange CA 92868, USA. mkenney@uci.edu
Abstract:
Keratoconus, a non-inflammatory thinning of the cornea, is a leading indication for corneal transplantation. For its causation, we propose a "Cascade Hypothesis" stating that keratoconus corneas have abnormal or defective enzymes in the lipid peroxidation and/or nitric oxide pathways leading to oxidative damage. The accumulation of oxidative, cytotoxic by-products causes an alteration of various corneal proteins, triggering a cascade of events, (i.e. apoptosis, altered signaling pathways, increased enzyme activities, fibrosis). This hypothesis is supported by biochemical, immunohistochemical and molecular data presented in this review. Based upon this evidence, one can speculate that keratoconus patients should minimize their exposure to oxidative stress. Protective steps should include wearing ultraviolet (UV) protection (in the contact lenses and/or sunglasses), minimizing the mechanical trauma (eye rubbing, poorly fit contact lenses) and keeping eyes comfortable with artificial tears, non-steroidal anti-inflammatory drugs and/or allergy medications.
Insights
Keratoconus, a corneal thinning condition, may stem from defective enzymes causing oxidative damage. Patients should minimize UV exposure and eye rubbing to protect their corneas.
Area of Science:
- Ophthalmology
- Biochemistry
- Cell Biology
Background:
- Keratoconus is a progressive, non-inflammatory thinning of the cornea.
- It is a primary indication for corneal transplantation.
- The exact causes of keratoconus remain incompletely understood.
Purpose of the Study:
- To propose a novel "Cascade Hypothesis" for the causation of keratoconus.
- To explain the role of oxidative stress in keratoconus pathogenesis.
- To review supporting biochemical, immunohistochemical, and molecular data.
Main Methods:
- Review of existing biochemical data.
- Analysis of immunohistochemical findings.
- Evaluation of molecular biology studies.
Main Results:
- Keratoconus corneas exhibit abnormal enzymes in lipid peroxidation and/or nitric oxide pathways.
- This leads to oxidative damage and accumulation of cytotoxic by-products.
- Oxidative stress triggers a cascade of events including apoptosis, altered signaling, and fibrosis.
Conclusions:
- The "Cascade Hypothesis" provides a framework for understanding keratoconus development.
- Minimizing oxidative stress is crucial for keratoconus patients.
- Protective measures include UV protection, reduced eye rubbing, and proper eye care.
Related Concept Videos
01:25Glaucoma: Overview
01:07MAPK Signaling Cascades