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A Reversible Silicon Oil-Induced Ocular Hypertension Model in Mice
Published on: November 15, 2019
Comparison of RCI001 and corticosteroid on the effects on intraocular pressure in mice
Soo Hyun Kim1, Young-Ah Ku2, Chungkwon Yoo1
1Department of Ophthalmology, Korea University College of Medicine, Seoul, Republic of Korea.
Purpose:
RCI001, a novel therapeutic candidate for the treatment of ocular inflammatory diseases, have demonstrated remarkable anti-inflammatory and antioxidant effects in various ocular experimental models. This study was to evaluate the effects of RCI001 on intraocular pressure (IOP) and compare them with those of corticosteroids in experimental mouse models.
Methods:
Experimental mice were randomly divided into naïve, phosphate-buffered saline (PBS), 0.1% dexamethasone (DEX-1), and 1% RCI001 (RCI) groups, and each reagent was pipetted into the right eye of the mouse at 10 μL thrice daily for 5 weeks. In addition, 20 μL of 0.1% dexamethasone was injected subconjunctivally into the right eye once weekly for 5 weeks in the DEX-2 group. The IOP was measured under anesthesia at baseline and twice weekly for 5 weeks. The △IOP (%) was defined as the change in IOP from baseline [△IOP (%) = (IOP-IOP)/IOP × 100%]. The anterior segments were clinically and histologically examined.
Results:
There was no significant increase in IOP and △IOP (%) [values by week 3 (day 21) in any of the groups]. However, IOP and △IOP (%) in the DEX-2 group tended to increase slightly after day 10 compared with baseline. Compared with baseline IOP values, the DEX-1 group showed a statistically significant increase in IOP at weeks 4 and 5, and the DEX-2 group at week 5. The △IOP (%) of the DEX-1 and DEX-2 groups (%) at week 5 were 38.2% ± 5.8% and 38.4 ± 4.6%, respectively. However, the IOP in the RCI group did not increase significantly until week 5. The RCI group did not show notable corneal changes, such as epithelial defects or stromal opacities, at week 5. In addition, hematoxylin and eosin (H&E) staining of corneas in the RCI group revealed healthy corneal epithelial, stromal, and endothelial integrity.
Conclusion:
Long-term use of RCI001 did not induce significant IOP elevation or ocular surface changes, whereas topical corticosteroids significantly increased the IOP. Therefore, RCI001 may be an effective anti-inflammatory agent with a low risk of drug-induced IOP elevation.
Insights
RCI001, an anti-inflammatory agent, did not significantly increase intraocular pressure (IOP) in mice over 5 weeks. Unlike corticosteroids, RCI001 shows a low risk of drug-induced IOP elevation, suggesting its potential for treating ocular inflammatory diseases.
Area of Science:
- Ophthalmology
- Pharmacology
- Drug Discovery
Background:
- Ocular inflammatory diseases require effective treatments.
- Corticosteroids are commonly used but can elevate intraocular pressure (IOP).
- RCI001 is a novel therapeutic candidate with demonstrated anti-inflammatory and antioxidant effects.
Purpose of the Study:
- To evaluate the effects of RCI001 on intraocular pressure (IOP) in experimental mouse models.
- To compare the IOP-altering effects of RCI001 with those of corticosteroids.
Main Methods:
- Mice were divided into groups receiving RCI001, dexamethasone (corticosteroid), or vehicle (PBS).
- Ocular treatments were administered topically and/or subconjunctivally for 5 weeks.
- Intraocular pressure (IOP) was measured regularly, and anterior segments were examined clinically and histologically.
Main Results:
- Topical and subconjunctival dexamethasone significantly increased IOP compared to baseline.
- RCI001 did not induce a significant increase in IOP over the 5-week treatment period.
- RCI001 treatment did not result in notable corneal changes or compromise corneal integrity.
Conclusions:
- Long-term use of RCI001 did not elevate IOP or cause ocular surface changes.
- Topical corticosteroids significantly increased IOP in the experimental models.
- RCI001 presents a potential anti-inflammatory agent for ocular diseases with a reduced risk of IOP elevation.
