The progressive blindness of glaucoma arises from pressure damage to the retina, the proximate cause being the presence of too much aqueous humor in the eye. The underlying causes are more complex and less well understood. As is the case for raised blood pressure, however, there are any number of ways to influence relevant mechanisms in order to control pressure without actually addressing the root cause damage and dysfunction of aging. Here, for example, researchers interfere in the expression of proteins critical in the production of aqueous humor, resulting in reduced pressure in the eye.
Glaucoma is a major global cause of irreversible vision loss. It is marked by elevated intraocular pressure (IOP) and the loss of retinal ganglion cells (RGC). While there are medical and surgical therapies for glaucoma aiming to reduce aqueous humor production or enhance its drainage, these treatments are often inadequate for effectively managing the disease.
In this study, we developed a targeted therapy for glaucoma by knocking down two genes associated with aqueous humor production (aquaporin 1, AQP1, and carbonic anhydrase type 2, CA2) using Cas13 RNA editing systems. We demonstrate that knockdown of AQP1 and CA2 significantly lowers IOP in wild-type mice and in a corticosteroid-induced glaucoma mouse model. We show that the lowered IOP results from decreasing aqueous production without affecting the outflow facility; this treatment also significantly promotes RGC survival as compared with untreated control groups.
Therefore, CRISPR-Cas-based gene editing may be an effective treatment to lower IOP for glaucomatous optic neuropathy.
Link: https://doi.org/10.1093/pnasnexus/pgaf168
View the full article at FightAging
