Faculty Collaboration Database

Longitudinal evaluation of expression of virally delivered transgenes in gerbil cone photoreceptors. Vis Neurosci 2008;25(3):273-82

Date

07/05/2008

Pubmed ID

18598398

Pubmed Central ID

PMC2643299

DOI

10.1017/S0952523808080577

Scopus ID

2-s2.0-46749138311 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Delivery of foreign opsin genes to cone photoreceptors using recombinant adeno-associated virus (rAAV) is a potential tool for studying the basic mechanisms underlying cone based vision and for treating vision disorders. We used an in vivo retinal imaging system to monitor, over time, expression of virally-delivered genes targeted to cone photoreceptors in the Mongolian gerbil (Meriones unguiculatus). Gerbils have a well-developed photopic visual system, with 11-14% of their photoreceptors being cones. We used replication deficient serotype 5 rAAV to deliver a gene for green fluorescent protein (GFP). In an effort to direct expression of the gene specifically to either S or M cones, the transgene was under the control of either the human X-chromosome opsin gene regulatory elements, i.e., an enhancer termed the locus control region (LCR) and L promoter, or the human S-opsin promoter. Longitudinal fluorescence images reveal that gene expression is first detectable about 14 days post-injection, reaches a peak after about 3 months, and is observed more than a year post-injection if the initial viral concentration is sufficiently high. The regulatory elements are able to direct expression to a subpopulation of cones while excluding expression in rods and non-photoreceptor retinal cells. When the same viral constructs are used to deliver a human long-wavelength opsin gene to gerbil cones, stimulation of the introduced human photopigment with long-wavelength light produces robust cone responses.

Author List

Mauck MC, Mancuso K, Kuchenbecker JA, Connor TB, Hauswirth WW, Neitz J, Neitz M

Author

Thomas B. Connor MD 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
Dependovirus
Electroretinography
Genetic Vectors
Gerbillinae
Green Fluorescent Proteins
Longitudinal Studies
Male
Microscopy, Confocal
Retinal Cone Photoreceptor Cells
Time Factors
Transgenes