Friday, November 22, 2024
11/22/2024
ABSTRACT Cataracts, a clouding of the natural lens, is the leading cause of blindness worldwide, with a projected 40M cases by 2050. Underrepresented groups and medically underserved populations are disproportionately impacted by cataracts. Clinical treatment is limited to surgical removal of the cataractous lens, and implantation of an intraocular lens (IOL). Unfortunately, the IOL is highly susceptible to growth from residual lens epithelial cells (LECs), a complication known as posterior capsule opacification (PCO) that occurs in ~40% of adult IOL patients. Laser capsulotomy surgery is used to treat PCO, but has significant potential side effects. The proposed work will lead to the development of “LEC-resistant IOLs” based on a new amphiphilic silicone, reducing the incidence of PCO and the need for a 2nd surgery (laser capsulotomy). This work is significant given not only the expected exceptional LEC-resistance and retention of desired opto-mechanical properties of the proposed IOLs (supported by preliminary data), but also that it relies on a strategy readily integrated into existing IOL materials, designs, and manufacturing processes. Diphenyl silicones are used to prepare foldable IOLs, wherein the elastomeric nature provides the ability to fold the IOL upon implantation such that the incision size may be reduced. In this work, new amphiphilic surface-modifying additives (SMAs) [developed by the PI], comprised of a poly(ethylene oxide) (PEO) segment and siloxane tether, will be readily blended into an IOL-type diphenyl silicone. These SMAs uniquely afford rapid and substantial migration to the aqueous/biological interface to produce LEC-resistance, without impacting opto-mechanical properties. The innovation of this work rests not only in the novelty of the PI-developed SMAs, but in the departure from other strategies that have attempted to produce IOLs with resistance to LEC growth (e.g., change to IOL geometric design, complex surface treatment, and reactive oxygen species (ROS)-producing modifiers). The approach to accomplish this work relies on a systematic and robust methods, and will be led by a team of skilled experts. In Aim 1 [led by Grunlan, PI], silicone formulations will be prepared with SMAs of varying structure and concentration in the diphenyl silicone, key material properties assessed, and IOLs prepared from formulations meeting success criteria. In Aim 2 [led by Chandler, Co-I] select formulations will be evaluated for resistance to LEC growth, and select IOLs assessed ex vivo in rabbit and human eyes with a commercial silicone IOL used as a control. Following iterations of Aim 1 and 2, in Aim 3 [led by Scott, Co-I), a SMA-modified IOL will be evaluated in a rabbit model, and biocompatibility and resistance to LEC growth compared to the commercial IOL. The clinical consultant, Dr. Lee, M.D. (a comprehensive ophthalmologist and ocular pathologist) will provide guidance to these studies.
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