Spatially Defined Latrunculin A-Eluting Intraocular Lenses Attenuate Posterior Capsule Opacification via Cytoskeletal Disruption.

Posterior capsule opacification (PCO), driven by the aberrant proliferation, migration, and fibrotic transformation of residual lens epithelial cells (LECs), remains the most common long-term complication of cataract surgery. Given that intraocular lenses (IOLs) are precision optical implants, anti-PCO surface modifications should balance localized therapeutic delivery with preservation of a clear central optical zone. Here, we developed spatially defined Latrunculin A (LatA)-eluting IOLs using a mask-assisted spin-coating strategy to deposit a concentric annular poly (lactic-co-glycolic acid) (PLGA) coating on the IOL periphery while leaving the central optical zone uncoated. We characterized the in vitro LatA release profile from the annular coating over a 28-day period. At concentrations of 100-200 nM, LatA suppressed LEC proliferation, migration, and fibrotic marker expression. LatA treatment disrupted F-actin organization and was associated with transcriptomic changes enriched in cytoskeletal remodeling and mechanotransduction pathways. In a rabbit cataract surgery model, LatA-functionalized IOLs significantly attenuated postoperative PCO during a 28-day follow-up period compared with unmodified and PLGA-coated IOL controls, with an aqueous humor LatA concentration of 129.85 ± 8.11 nM at day 28 and no detectable adverse intraocular responses over the follow-up period. These findings provide preliminary support for spatially defined LatA-eluting IOLs as a cytoskeleton-targeting approach to attenuate PCO while preserving an uncoated central optical zone. STATEMENT OF SIGNIFICANCE: A precisely defined concentric annular LatA-eluting PLGA coating was fabricated on IOL surfaces using mask-assisted spin coating to achieve localized drug delivery while preserving the central optical zone. Low-dose LatA attenuates the fibrotic phenotype of LECs by disrupting actin cytoskeletal remodeling. A rabbit PCO model provides preliminary in vivo evidence that this strategy attenuates PCO development. These findings suggest that functionalized IOLs may have potential translational value for the prevention of PCO.