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Published on: April 3, 2016
Suppression of post-vitrectomy lens changes in the rabbit by novel benzopyranyl esters and amides
J R Kuszak1, J G Sivak, K L Moran
1Department of Ophthalmology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA.
Abstract:
This study reports for the first time a therapeutic modality for the suppression of posterior subcapsular cataract (PSC) formation in an animal model (rabbit) of vitrectomy. This therapeutic modality may also have the potential to attenuate/prevent the high incidence of loss of vision due to cataract formation in patients that undergo vitrectomy. Unilateral, partial vitrectomy was performed on 2.5 month old Dutch Belted rabbits with vitreous replaced by either commercially available BSS((R)) or BSS PLUS((R)) (n=16). Alternatively, vitreous was replaced with a proprietary, modified BSS PLUS((R)) irrigating solution containing 1.25 microM AL-8417 (n=12), 5.0 microM AL-12615 (n=5) or 5.0 microM AL-17052 (n=9). Age matched, non-operated rabbits were used as controls (n=16). Lenses were analysed by correlative structural (light, scanning electron microscopic and three-dimensional computer-assisted drawings) and optical (low power helium-neon laser scan) quality analysis 6 months following surgery. Results demonstrate that vitreous replacement with an irrigating solution that contains the ester-linked benzopyran, AL-8417, the amide-linked benzopyran pro-drug, AL-17052, or its active metabolite, AL-12615, prevented abnormal post-vitrectomy lens growth, or fiber formation. Focal length variability (FLV) assessments (sharpness of focus) confirmed the beneficial drug effects detected morphologically, with FLV being essentially equal to that of age-matched, non-surgical controls. In contrast, lenses of animals with vitreous replaced solely with BSS((R)) or BSS PLUS((R)) exhibited significantly higher FLV than both age-matched controls and animals that underwent vitrectomy with drug-containing irrigating solutions. The ability of AL-8417, AL-17052 and its active metabolite, AL-12615, to suppress vitrectomy-induced posterior lens fiber changes appears to reside in their unique pharmacological profile, acting as antioxidant, anti-inflammatory and cytostatic agents.
Insights
New therapeutic agents, AL-8417 and its related compounds, effectively prevent posterior subcapsular cataract (PSC) formation after vitrectomy in rabbits. These compounds show potential for preventing vision loss in patients undergoing vitrectomy surgery.
Area of Science:
- Ophthalmology
- Pharmacology
- Biomedical Engineering
Background:
- Posterior subcapsular cataract (PSC) is a common complication following vitrectomy surgery, leading to vision loss.
- Current irrigating solutions like BSS and BSS PLUS do not prevent post-vitrectomy cataract formation.
Purpose of the Study:
- To evaluate the efficacy of novel therapeutic agents (AL-8417, AL-12615, AL-17052) in preventing PSC formation in a rabbit vitrectomy model.
- To assess the potential of these agents to maintain lens clarity and visual function post-vitrectomy.
Main Methods:
- Unilateral partial vitrectomy was performed on Dutch Belted rabbits.
- Vitreous was replaced with standard irrigating solutions (BSS, BSS PLUS) or modified BSS PLUS containing AL-8417, AL-12615, or AL-17052.
- Lenses were analyzed structurally and optically 6 months post-surgery; focal length variability (FLV) was measured.
Main Results:
- Vitreous replacement with AL-8417, AL-12615, or AL-17052 prevented abnormal lens fiber formation post-vitrectomy.
- FLV measurements confirmed the beneficial effects of these drugs, with values similar to non-surgical controls.
- Control groups receiving only BSS or BSS PLUS showed significantly higher FLV, indicating impaired lens function.
Conclusions:
- The benzopyran derivatives AL-8417, AL-17052, and AL-12615 effectively suppress vitrectomy-induced posterior lens changes in rabbits.
- These agents act as antioxidants, anti-inflammatories, and cytostatics, offering a promising therapeutic strategy for preventing post-vitrectomy cataracts.
- This study highlights a potential new treatment to mitigate vision loss associated with vitrectomy surgery.
