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Leonid M Zukin, Michelle G Pedler, Biehuoy Shieh, Sarah Seiwald, J. Mark Petrash; The role of aldose reductase in lens regeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1206.
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© ARVO (1962-2015); The Authors (2016-present)
After cataract surgery, the residual layer of lens epithelial cells lining the anterior capsule can undergo several different responses, including fibrosis and lens fiber cell differentiation. The fibrotic response leads to posterior capsular opacification (PCO), while the lens fiber cell differentiation response can lead to regeneration of lens material. While we previously demonstrated that the PCO response can be suppressed with aldose reductase (AR) inhibitors, follow up studies described here revealed unexpectedly higher levels of lens regeneration in AR deficient mice (ARKO) following extracapsular lens extraction (ECLE).
The entire lens was removed from one eye of C57BL/6 (WT), AR-transgenic (AR-Tg), and ARKO mice using an ECLE procedure. Whole eyes were harvested up to 8 weeks postoperatively and stained with either hematoxylin and eosin or immunostained for crystallins and the fibrosis marker α-smooth muscle actin (α-SMA). To ensure consistency, all eyes examined for lens regeneration were completely sectioned in the coronal plane and slides were chosen that showed the regenerated lens material in its largest dimension.
Five days after ECLE, all mouse strains exhibited robust αA-crystallin staining within the capsular bag, but ARKO lens capsules demonstrated substantially less staining for α-SMA. This suggested that lack of AR suppresses the fibrotic response in the immediate postoperative period, but not the lens fiber differentiation pathway. Eight weeks after ECLE, ARKO mice eyes contained a regenerated intracapsular, γ-crystallin positive lens-like structure, exhibiting a circular shape and bow region with elongated, nucleated cells (Panel A). Although WT and AR-Tg eyes also produced an intracapsular, γ-crystallin positive mass after ECLE, their structures were smaller, of irregular shape, and lacked recognizable lens-like anatomy (Panels B and C, respectively). ARKO regenerated a lens-shaped structure 44% the size of its unoperated, contralateral lens, whereas WT and AR-Tg eyes only produced lens fiber masses 8% and 14% the size of their contralateral control eyes, respectively.
This study further validates the critical role of AR in the post-operative PCO response and its potential role in the regulation of lens regeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Legend: γ-crystallin staining of ARKO (A), WT (B), and AR-Tg (C) eyes 8 weeks post-ECLE.
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