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Preclinical Models of Rare Corneal and Ocular Surface Diseases: a Comprehensive Narrative Review
Erica A L Lecchi1, Ava Dashti2, Laura Frutos-Rincón3
1Eye Repair Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Abstract:
Rare eye diseases of the cornea and ocular surface (REDs) remain a clinical challenge owing to their low prevalence, heterogeneous presentation, and limited therapeutic options. As REDs mechanisms are often complex, preclinical models are essential to advance mechanistic understanding and support the development of targeted treatments. This review provides a comprehensive overview of the experimental platforms currently available to study REDs, including in vitro models such as primary and engineered cell systems, coculture approaches, and emerging 3D organoid technologies. In addition, we summarize in vivo strategies ranging from surgically induced models to genetic and transgenic systems that reproduce the relevant ocular phenotypes. By comparing the strengths, limitations, and translational value of these complementary approaches, this review offers an integrated perspective on how preclinical modeling can be optimized to investigate REDs pathophysiology. Furthermore, we highlight how emerging tools-such as organ-on-chip platforms and artificial intelligence-assisted analytics-may enhance model fidelity and accelerate the identification of effective therapeutic strategies.
Insights
This review explores preclinical models for rare eye diseases of the cornea and ocular surface (REDs). It compares various in vitro and in vivo strategies to advance understanding and treatment development for REDs.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Translational Research
Background:
- Rare eye diseases of the cornea and ocular surface (REDs) present significant clinical challenges due to their low prevalence and complex mechanisms.
- Limited therapeutic options necessitate advanced research tools for understanding REDs pathophysiology.
- Preclinical models are crucial for mechanistic insights and the development of targeted treatments for REDs.
Purpose of the Study:
- To provide a comprehensive overview of available experimental platforms for studying REDs.
- To compare the strengths, limitations, and translational value of various preclinical models.
- To offer an integrated perspective on optimizing preclinical modeling for REDs research.
Main Methods:
- Review of in vitro models including primary cells, engineered cell systems, cocultures, and 3D organoids.
- Summary of in vivo strategies such as surgically induced, genetic, and transgenic models.
- Analysis of emerging tools like organ-on-chip platforms and AI-assisted analytics.
Main Results:
- Various in vitro and in vivo models exist for REDs research, each with unique advantages and disadvantages.
- A comparative analysis highlights the translational potential of different experimental approaches.
- Emerging technologies show promise for enhancing model fidelity and accelerating therapeutic discovery.
Conclusions:
- Optimizing preclinical models is key to advancing the mechanistic understanding of REDs.
- Integrated approaches combining different model systems can enhance research efficacy.
- Novel technologies like organ-on-chip and AI are poised to revolutionize REDs research and treatment development.
