Faculty Collaboration Database

Late gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa. Nat Commun 2023 Dec 12;14(1):8256

Date

12/13/2023

Pubmed ID

38086857

Pubmed Central ID

PMC10716155

DOI

10.1038/s41467-023-44063-8

Scopus ID

2-s2.0-85179645989 (requires institutional sign-in at Scopus site)

Abstract

Retinitis pigmentosa is an inherited photoreceptor degeneration that begins with rod loss followed by cone loss. This cell loss greatly diminishes vision, with most patients becoming legally blind. Gene therapies are being developed, but it is unknown how retinal function depends on the time of intervention. To uncover this dependence, we utilize a mouse model of retinitis pigmentosa capable of artificial genetic rescue. This model enables a benchmark of best-case gene therapy by removing variables that complicate answering this question. Complete genetic rescue was performed at 25%, 50%, and 70% rod loss (early, mid and late, respectively). Early and mid treatment restore retinal output to near wild-type levels. Late treatment retinas exhibit continued, albeit slowed, loss of sensitivity and signal fidelity among retinal ganglion cells, as well as persistent gliosis. We conclude that gene replacement therapies delivered after 50% rod loss are unlikely to restore visual function to normal. This is critical information for administering gene therapies to rescue vision.

Author List

Scalabrino ML, Thapa M, Wang T, Sampath AP, Chen J, Field GD

Author

Miranda L. Scalabrino PhD Assistant Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Genetic Therapy
Humans
Mice
Retina
Retinal Cone Photoreceptor Cells
Retinal Degeneration
Retinitis Pigmentosa