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Development of Animal Models for Lens and Corneal Diseases Using N-Methyl-N-Nitrosourea
Yingxin Qu1,1, Runpu Li1, Xiaoqi Li1
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Purpose:
N-methyl-N-nitrosourea (MNU) is an alkylating toxicant with potent mutagenic ability. This study was designed to induce apoptosis in lens epithelial cells (LECs) and corneal endothelial cells (CECs) via MNU administration. We sought to build ocular disease models of cataract and corneal endothelial decompensation.
Methods:
MNU was delivered into the intraperitoneal cavities of neonatal rats and the anterior chambers of adult rabbits. The MNU-treated animals were then subjected to a series of functional and morphological analyses at various time points.
Results:
MNU treatment induced pervasive apoptosis of LECs and CECs. These effects were dose and time dependent. Mature cataracts were found in neonatal rats 3 weeks after MNU treatment. Histological analysis revealed that MNU toxicity induced swelling, vacuolation, and liquefaction in lens fibers of MNU-treated rats. Pentacam examination showed that the average density of rat lens increased significantly after MNU administration. Terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) analysis showed pervasive apoptotic staining in the lenses of MNU-treated rats. In rabbit eyes, intracameral treatment with MNU induced corneal edema and significantly increased central corneal thickness, which peaked at P14. Morphological and immunohistochemical analysis showed that CECs were effectively ablated in the MNU-treated rabbits. The expression of 8-OHdG increased significantly in the cornea of MNU-treated rabbits, compared with vehicle-treated controls.
Conclusions:
MNU is sufficient to induce ocular cell apoptosis in animal models. These models of MNU-induced cataract and corneal endothelial decompensation represent valuable tools for efforts to develop relevant therapies.
Insights
N-methyl-N-nitrosourea (MNU) induces apoptosis in ocular cells, creating animal models for cataract and corneal decompensation. These models are valuable for developing new therapies for these eye conditions.
Area of Science:
- Ophthalmology
- Toxicology
- Cell Biology
Background:
- N-methyl-N-nitrosourea (MNU) is a potent mutagenic alkylating toxicant.
- Ocular diseases like cataracts and corneal decompensation significantly impact vision.
- Developing reliable animal models is crucial for understanding disease mechanisms and testing therapies.
Purpose of the Study:
- To induce apoptosis in lens epithelial cells (LECs) and corneal endothelial cells (CECs) using MNU.
- To establish animal models for MNU-induced cataract and corneal endothelial decompensation.
- To evaluate the dose and time dependency of MNU's ocular toxicity.
Main Methods:
- Neonatal rats received intraperitoneal MNU injections; adult rabbits received intracameral MNU injections.
- Functional and morphological analyses were performed at various time points post-treatment.
- Techniques included Pentacam examination, TUNEL staining, and immunohistochemistry for 8-OHdG.
Main Results:
- MNU treatment led to dose- and time-dependent apoptosis of LECs and CECs.
- Neonatal rats developed mature cataracts, with histological evidence of lens fiber damage.
- Rabbits showed corneal edema, increased corneal thickness, and significant ablation of CECs, with elevated 8-OHdG expression.
Conclusions:
- MNU effectively induces ocular cell apoptosis in established animal models.
- These MNU-induced models of cataract and corneal decompensation are valuable for therapeutic development.
- Further research using these models can advance treatments for vision-impairing ocular conditions.
