Cataracts, defined as any opacity in the lens, remains the leading cause of blindness in the world. Cataracts can be caused by a variety of factors, including genetic mutations, trauma to the eye, inflammation in the eye, long term use of steroids, metabolic disorders (including diabetes) and everyday exposure to UV light or radiation.
The only treatment for cataracts is surgery. Cataract surgery is the #1 Medicare cost and with an aging population, it is imperative to develop non-surgical treatments. While it is a procedure commonly performed in the United States, cataract surgery is not without risk. Cataract surgery increases the risk of retinal detachment, infection, bleeding inside the eye, corneal/retinal swelling, increased intraocular pressure and droopy eyelid. About half of cataract surgery patients require more treatment for post-surgical secondary cataracts most commonly caused by posterior capsular opacification (PCO).
A growing number of studies, including our research, have linked Eph-ephrin bidirectional signaling to congenital and age-related cataracts in humans and mice. Our work has revealed that the EphA2 receptor is required for hexagonal cell shape of epithelial and fiber cells while the ephrin-A5 ligand is needed for maintaining the quiescence of epithelial cells. Our latest work determined that EphA2 and ephrin-A5 are not a lens receptor-ligand pair using a genetic approach. We are working to determine which ephrin ligand partners with EphA2 to organize equatorial epithelial cells and which Eph receptor binds to ephrin-A5 to maintain the anterior epithelium. There is little known about which other Ephs and ephrins are expressed and utilized in the lens. Our goal is to dissect the cellular and mechanisms for cataractogenesis due to Eph-ephrin dysfunction to find new drug treatment targets to prevent or delay cataracts and PCO.
